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  • 1.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Niklas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Söderlund, Karin
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Buren, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training2014In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 114, no 7, p. 1463-1471Article in journal (Refereed)
    Abstract [en]

    The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1 alpha, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 +/- A 6.1 to 61.9 +/- A 6.2 kg), VO2 peak (from 49.7 +/- A 5.5 to 56.3 +/- A 5.0 ml/kg/min), and fat oxidation (from 6.8 +/- A 2.1 to 9.1 +/- A 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.

  • 2.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Goedecke, Julia
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The human visceral fat depot has a unique inflammatory profile2010In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 18, no 5, p. 879-883Article in journal (Refereed)
    Abstract [en]

    Obesity can be considered as a low-grade inflammatory condition, strongly linked to adverse metabolic outcomes. Obesity-associated adipose tissue inflammation is characterized by infiltration of macrophages and increased cytokine and chemokine production. The distribution of adipose tissue impacts the outcomes of obesity, with the accumulation of fat in visceral adipose tissue (VAT) and deep subcutaneous adipose tissue (SAT), but not superficial SAT, being linked to insulin resistance. We hypothesized that the inflammatory gene expression in deep SAT and VAT is higher than in superficial SAT. A total of 17 apparently healthy women (BMI: 29.3 +/- 5.5 kg/m2) were included in the study. Body fat (dual-energy X-ray absorptiometry) and distribution (computed tomography) were measured, and insulin sensitivity, blood lipids, and blood pressure were determined. Inflammation-related differences in gene expression(real-time PCR) from VAT, superficial and deep SAT biopsies were analyzed using univariate and multivariate data analyses. Using multivariate discrimination analysis, VAT appeared as a distinct depot in adipose tissue inflammation,while the SAT depots had a similar pattern, with respect to gene expression. A significantly elevated (P < 0.01)expression of the CC chemokine receptor 2 (CCR2) and macrophage migration inhibitory factor (MIF) in VAT contributed strongly to the discrimination. In conclusion, the human adipose tissue depots have unique inflammatory patterns, with CCR2 and MIF distinguishing between VAT and the SAT depots.

  • 3.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomquist, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, Christel
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sandberg, Susanne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Ingegerd, Söderström
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Decreased TLR4 and Increased MIF Adipose Gene Expression Following Long-Term Diet InterventionManuscript (preprint) (Other academic)
  • 4.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Simonyte, Kotryna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersson, Therése
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rask, Eva
    Örebro Univ Hosp, Dept Med, Örebro, Sweden.
    Mattsson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women2012In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, no 5, p. 684-690Article in journal (Refereed)
    Abstract [en]

    Objective:  The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease which are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared to premenopausal women. We also wanted to determine if these markers are reduced by stable weight loss in obese women. Design and methods:  Anthropometric data, blood samples, and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. Results:  IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal versus premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal versus premenopausal women. Two years after gastric bypass surgery, adipose expression of IL-8, tumor necrosis factor-α, and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before gastric bypass surgery, but these associations disappeared after surgery. Conclusion:  Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss. © 2011 Blackwell Publishing Ltd.

  • 5.
    Andersson, Therése
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Simonyte, Kotryna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andrew, Ruth
    Strand, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Walker, Brian R
    Mattsson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women2009In: PloS one, ISSN 1932-6203, Vol. 4, no 12, p. e8475-Article in journal (Refereed)
    Abstract [en]

    With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

  • 6.
    Blomquist, Caroline
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Alvehus, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, Christel
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden..
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Mellberg, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity2017In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 25, no 5, p. 892-900Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Abdominal fat accumulation after menopause is associated with low-grade inflammation and increased risk of metabolic disorders. Effective long-term lifestyle treatment is therefore needed.

    METHODS: Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation-related parameters.

    RESULTS: Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long-term significant effects (P < 0.001) on adipose gene expression were found for toll-like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity C-reactive protein was decreased in the PD group at 24 months (P = 0.001).

    CONCLUSIONS: A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression.

  • 7.
    Boman, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Gene expression and fiber type variations in repeated vastus lateralis biopsies2015In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 52, no 2, p. 812-817Article in journal (Refereed)
    Abstract [en]

    Introduction: Muscle sample collection can introduce variation in any measured variable due to inter- and intramuscle variation. We investigated the variation in gene expression and fiber type composition after repeated biopsy sampling from the vastus lateralis muscle. Methods: Six subjects donated 3 tissue samples each. One hour after baseline sampling from 1 vastus lateralis muscle, samples from both vastus lateralis muscles were obtained. Results: The fiber type composition differed between biopsies taken from the same leg. There were no within-subject differences in gene expression between the 3 biopsies. Multivariate analysis supports a model in which gene expression differs significantly between individuals but is not affected by repeated muscle biopsy sampling from the same subject. Conclusion: One vastus lateralis muscle sample per subject is sufficient to establish a reliable baseline for comparing gene expression representing selected pathways over time within the same individual.

  • 8.
    Boman, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åkerfeldt, T
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
    Effects of protein ingestion on the hormonal response to resistance exercise and increases in lean body mass after eight weeks of trainingManuscript (preprint) (Other academic)
  • 9.
    Buren, Jonas
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Bergström, Sven-Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Loh, Edmund
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Mattsson, Cecilia
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Hippocampal 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression has a diurnal variability that is lost in the obese Zucker rat.2007In: Endocrinology, ISSN 0013-7227, Vol. 148, no 6, p. 2716-22Article in journal (Refereed)
  • 10.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Glucose and lipid metabolism in insulin resistance: an experimental study in fat cells2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 2 diabetes is usually caused by a combination of pancreatic β-cell failure and insulin resistance in target tissues like liver, muscle and fat. Insulin resistance is characterised by an impaired effect of insulin to reduce hepatic glucose production and to promote glucose uptake in peripheral tissues. The focus of this study was to further elucidate cellular mechanisms for insulin resistance that may be of relevance for type 2 diabetes in humans. We used rat and human adipocytes as an established model of insulin’s target cells.

    Glucocorticoids, e.g. cortisol, can induce insulin resistance in vivo. In the present study, pretreatment of rat adipocytes in vitro for 24 h with the cortisol analogue dexamethasone produced a downregulation of glucose uptake capacity as well as a marked depletion of cellular insulin receptor substrate 1 (IRS-1) and protein kinase B (PKB), two proteins suggested to play a critical role in the intracellular signal transduction pathway of insulin. The amount of phosphorylated PKB in response to acute insulin treatment was decreased in parallel to total PKB content. The basal rate of lipolysis was enhanced, but insulin’s antilipolytic effect was not consistently altered following dexamethasone pretreatment.

    Alterations in blood glucose as well as insulin levels may be of great importance for cellular as well as whole-body insulin resistance. High glucose (≥15 mM) for 24 h induced a decrease in glucose uptake capacity in rat adipocytes and IRS-1 content was reduced whereas IRS-2 was increased. Long-term pretreatment with a high insulin concentration downregulated insulin binding capacity and when combined with high glucose, it produced a pronounced

    reduction of cellular IRS-1 and 2 content together with insensitivity to insulin’s effect to activate PKB and a decrease in glucose uptake capacity. A common denominator for a decrease in glucose uptake capacity in our rat adipocyte studies seems to be a decrease in IRS-1 content.

    Adipocytes from type 2 diabetes patients are insulin-resistant, but in our work the insulin resistance could be reversed by incubation of the cells at a physiological glucose level for 24 h. Insulin resistance in fresh adipocytes from type 2 diabetes patients was associated with in vivo insulin resistance and glycemic level and with adipocyte cell size and waist-hip ratio

    (WHR).

    As a potential mechanism for postprandial dyslipidemia in type 2 diabetes, we examined the nutritional regulation of subcutaneous adipose tissue lipoprotein lipase (LPL) activity. It was upregulated by ~40-50 % after a standardised lipid-enriched meal and this was very similar in type 2 diabetes patients and control subjects, suggesting that the postprandial

    hypertriglyceridemia found in type 2 diabetes is not explained by an altered nutritional regulation of LPL in subcutaneous fat.

    In conclusion, the present work provides evidence for novel interactions between glucocorticoids and insulin in the regulation of glucose metabolism that may potentially contribute to the development of insulin resistance. High levels of glucose and insulin produce perturbations in the insulin signalling pathway that may be of relevance for human type 2 diabetes. Cellular insulin resistance may be secondary to the diabetic state in vivo, e.g. via glucotoxicity. This is supported by our finding that insulin resistance in adipocytes from type 2 diabetes patients can be reversed after incubation at a physiological glucose level.

    Key words: adipocyte, insulin resistance, type 2 diabetes, insulin signalling, glucose uptake,

    insulin, glucose, dexamethasone, insulin receptor substrate, protein kinase B, GLUT4,

    lipoprotein lipase.

  • 11.
    Burén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Is insulin resistance caused by defects in insulin's target cells or by a stressed mind?2005In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 21, no 6, p. 487-494Article in journal (Other academic)
    Abstract [en]

    The importance of understanding insulin action is emphasized by the increasing prevalence of insulin resistance in various populations and by the fact that it plays an important pathophysiological role in many common disorders, for example, diabetes, obesity, hypertension and dyslipidemia. The primary factors responsible for the development of insulin resistance are so far unknown, although both genetic and environmental factors are involved. The genetic defects responsible for the common forms of insulin resistance, for example, in type 2 diabetes, are largely unidentified. Some studies from our group as well as by other investigators suggest that cellular insulin resistance is reversible and that it may be secondary to factors in the in vivo environment. These may include insulin-antagonistic action of hormones like catecholamines, glucocorticoids, sex steroids and adipokines as well as dysregulation of autonomic nervous activity and they could contribute to the early development of insulin resistance. Some of these factors can directly impair glucose uptake capacity and this might be due to alterations in key proteins involved in insulin's intracellular signaling pathways. This article briefly summarizes proposed mechanisms behind cellular and whole-body insulin resistance. In particular, we question the role of intrinsic defects in insulin's target cells as primary mechanisms in the development of insulin resistance in type 2 diabetes and we suggest that metabolic and neurohormonal factors instead are the main culprits.

  • 12.
    Burén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lai, Y C
    Lundgren, Magdalena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Jan W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jensen, J
    Insulin action and signalling in fat and muscle from dexamethasone-treated rats2008In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 474, no 1, p. 91-101Article in journal (Refereed)
    Abstract [en]

    Glucocorticoids initiate whole body insulin resistance and the aim of the present study was to investigate effects of dexamethasone on protein expression and insulin signalling in muscle and fat tissue. Rats were injected with dexamethasone (1mg/kg/day, i.p.) or placebo for 11 days before insulin sensitivity was evaluated in vitro in soleus and epitrochlearis muscles and in isolated epididymal adipocytes. Dexamethasone treatment reduced insulin-stimulated glucose uptake and glycogen synthesis by 30-70% in epitrochlearis and soleus, and insulin-stimulated glucose uptake by approximately 40% in adipocytes. 8-bromo-cAMP-stimulated lipolysis was approximately 2-fold higher in adipocytes from dexamethasone-treated rats and insulin was less effective to inhibit cAMP-stimulated lipolysis. A main finding was that dexamethasone decreased expression of PKB and insulin-stimulated Ser(473) and Thr(308) phosphorylation in both muscles and adipocytes. Expression of GSK-3 was not influenced by dexamethasone treatment in muscles or adipocytes and insulin-stimulated GSK-3beta Ser(9) phosphorylation was reduced in muscles only. A novel finding was that glycogen synthase (GS) Ser(7) phosphorylation was higher in both muscles from dexamethasone-treated rats. GS expression decreased (by 50%) in adipocytes only. Basal and insulin-stimulated GS Ser(641) and GS Ser(645,649,653,657) phosphorylation was elevated in epitrochlearis and soleus muscles and GS fractional activity was reduced correspondingly. In conclusion, dexamethasone treatment (1) decreases PKB expression and insulin-stimulated phosphorylation in both muscles and adipocytes, and (2) increases GS phosphorylation (reduces GS fractional activity) in muscles and decreases GS expression in adipocytes. We suggest PKB and GS as major targets for dexamethasone-induced insulin resistance.

  • 13.
    Burén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lindmark, Stina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Jan W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    In vitro reversal of hyperglycemia normalizes insulin action in fat cells from type 2 diabetes patients: is cellular insulin resistance caused by glucotoxicity in vivo?2002In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 52, no 2, p. 239-245Article in journal (Refereed)
    Abstract [en]

    Chronic hyperglycemia promotes the development of insulin resistance. The aim of this study was to investigate whether cellular insulin resistance is secondary to the diabetic state in human type 2 diabetes. Subcutaneous fat biopsies were taken from 3 age-, sex-, and body mass index (BMI)-matched groups with 10 subjects in each group: type 2 diabetes patients with either good (hemoglobin A1c [HbA1c] [lt ] 7%, G) or poor (HbA1c [gt ] 7.5%, P) metabolic control and healthy control subjects (C). Insulin action in vitro was studied by measurements of glucose uptake both directly after cell isolation and following a 24-hour incubation at a physiological glucose level (6 mmol/L). The relationship with insulin action in vivo was addressed by employing the euglycemic clamp technique. Freshly isolated fat cells from type 2 diabetes patients with poor metabolic control had [sim ]55% lower maximal insulin response (1,000 [mu ]U/mL) on glucose uptake (P [lt ] .05) compared to C. Cells from P were more insulin-resistant (P [lt ] .05) than cells from G at a low (5 [mu ]U/mL) but not at a high (1,000 [mu ]U/mL) insulin concentration, suggesting insulin insensitivity. However, following 24 hours of incubation at physiological glucose levels, insulin resistance was completely reversed in the diabetes cells and no differences in insulin-stimulated glucose uptake were found among the 3 groups. Insulin sensitivity in vivo assessed with hyperinsulinemic, euglycemic clamp (M-value) was significantly associated with insulin action on glucose uptake in fresh adipocytes in vitro (r = 0.50, P [lt ] .01). Fasting blood glucose at the time of biopsy and HbA1c, but not serum insulin, were negatively correlated to insulin's effect to stimulate glucose uptake in vitro (r = [minus ]0.36, P = .064 and r = [minus ] 0.41, P [lt ].05, respectively) in all groups taken together. In the in vivo situation, fasting blood glucose, HbA1c, and serum insulin were all negatively correlated to insulin sensitivity (M-value; r = [minus ]0.62, P[lt ] .001, r= [minus ]0.61, P[lt ] .001, and r = [minus ]0.56, p [lt ] .01, respectively). Cell size, waist-to-hip ration (WHR), and BMI correlated negatively with insulin's effect to stimulate glucose uptake both in vitro (r = [minus ]0.55, P [lt ] .01, r = [minus ]0.54, P [lt ] .01, and r = [minus ]0.43, P [lt ] .05, respectively) and in vivo (r = [minus ]0.43, P [lt ] .05, r = [minus ]0.50, P [lt ] .01, and r = [minus ]0.36, P [lt ] .05, respectively). Multiple regression analyses revealed that adipocyte cell size and WHR independently predicted insulin resistance in vitro. Furthermore, insulin sensitivity in vivo could be predicted by fasting blood glucose and serum insulin levels. We conclude that insulin resistance in fat cells from type 2 diabetes patients is fully reversible following incubation at physiological glucose concentrations. Thus, cellular insulin resistance may be mainly secondary to the hyperglycemic state in vivo.

  • 14.
    Burén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Liu, Hui-Xia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jensen, J.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Jan W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dexamethasone impairs insulin signalling and glucose transport by depletion of insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase B in primary cultured rat adipocytes.2002In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 146, no 3, p. 419-429Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Glucocorticoid excess leads to insulin resistance. This study explores the effects of glucocorticoids on the glucose transport system and insulin signalling in rat adipocytes. The interaction between glucocorticoids and high levels of insulin and glucose is also addressed. DESIGN AND METHODS: Isolated rat adipocytes were cultured for 24 h at different glucose concentrations (5 and 15 mmol/l) with or without the glucocorticoid analogue dexamethasone (0.3 micromol/l) and insulin (10(4) microU/ml). After the culture period, the cells were washed and then basal and insulin-stimulated glucose uptake, insulin binding and lipolysis as well as cellular content of insulin signalling proteins (insulin receptor substrate-1 (IRS-1), IRS-2, phosphatidylinositol 3-kinase (PI3-K) and protein kinase B (PKB)) and glucose transporter isoform GLUT4 were measured. RESULTS: Dexamethasone in the medium markedly decreased both basal and insulin-stimulated glucose uptake at both 5 and 15 mmol/l glucose (by approximately 40-50%, P<0.001 and P<0.05 respectively). Combined long-term treatment with insulin and dexamethasone exerted additive effects in decreasing basal, and to a lesser extent insulin-stimulated, glucose uptake capacity (P<0.05) compared with dexamethasone alone, but this was seen only at high glucose (15 mmol/l). Insulin binding was decreased (by approximately 40%, P<0.05) in dexamethasone-treated cells independently of surrounding glucose concentration. Following dexamethasone treatment a approximately 75% decrease (P<0.001) in IRS-1 expression and an increase in IRS-2 (by approximately 150%, P<0.001) was shown. Dexamethasone also induced a subtle decrease in PI3-K (by approximately 20%, P<0.01) and a substantial decrease in PKB content (by approximately 45%, P<0.001). Insulin-stimulated PKB phosphorylation was decreased (by approximately 40%, P<0.01) in dexamethasone-treated cells. Dexamethasone did not alter the amount of total cellular membrane-associated GLUT4 protein. The effects of dexamethasone per se on glucose transport and insulin signalling proteins were mainly unaffected by the surrounding glucose and insulin levels. Dexamethasone increased the basal lipolytic rate (approximately 4-fold, P<0.05), but did not alter the antilipolytic effect of insulin. CONCLUSIONS: These results suggest that glucocorticoids, independently of the surrounding glucose and insulin concentration, impair glucose transport capacity in fat cells. This is not due to alterations in GLUT4 abundance. Instead dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 and PKB accompanied by a parallel reduction in insulin-stimulated activation of PKB.

  • 15.
    Burén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Liu, Hui-Xia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lauritz, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Jan W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    High glucose and insulin in combination cause insulin receptor substrate-1 and -2 depletion and protein kinase B desensitisation in primary cultured rat adipocytes: possible implications for insulin resistance in type 2 diabetes2003In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 148, p. 157-167Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The purpose of this study was to investigate the cellular effects of long-term exposure to high insulin and glucose levels on glucose transport and insulin signalling proteins. DESIGN AND METHODS: Rat adipocytes were cultured for 24 h in different glucose concentrations with 10(4) microU/ml of insulin or without insulin. After washing, (125)I-insulin binding, basal and acutely insulin-stimulated d-[(14)C]glucose uptake, and insulin signalling proteins and glucose transporter 4 (GLUT4) were assessed. RESULTS: High glucose (15 and 25 mmol/l) for 24 h induced a decrease in basal and insulin-stimulated glucose uptake compared with control cells incubated in low glucose (5 or 10 mmol/l). Twenty-four hours of insulin treatment decreased insulin binding capacity by approximately 40%, and shifted the dose-response curve for insulin's acute effect on glucose uptake 2- to 3-fold to the right. Twenty-four hours of insulin treatment reduced basal and insulin-stimulated glucose uptake only in the presence of high glucose (by approximately 30-50%). At high glucose, insulin receptor substrate-1 (IRS-1) expression was downregulated by approximately 20-50%, whereas IRS-2 was strongly upregulated by glucose levels of 10 mmol/l or more (by 100-400%). Insulin treatment amplified the suppression of IRS-1 when combined with high glucose and also IRS-2 expression was almost abolished. Twenty-four hours of treatment with high glucose or insulin, alone or in combination, shifted the dose-response curve for insulin's effect to acutely phosphorylate protein kinase B (PKB) to the right. Fifteen mmol/l glucose increased GLUT4 in cellular membranes (by approximately 140%) compared with 5 mmol/l but this was prevented by a high insulin concentration. CONCLUSIONS: Long-term exposure to high glucose per se decreases IRS-1 but increases IRS-2 content in rat adipocytes and it impairs glucose transport capacity. Treatment with high insulin downregulates insulin binding capacity and, when combined with high glucose, it produces a marked depletion of IRS-1 and -2 content together with an impaired sensitivity to insulin stimulation of PKB activity. These mechanisms may potentially contribute to insulin resistance in type 2 diabetes.

  • 16. Evans, Juliet
    et al.
    Goedecke, Julia H
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Alvehus, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomquist, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hayes, Philip M
    Adams, Kevin
    Dave, Joel A
    Levitt, Naomi S
    Lambert, Estelle V
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Depot- and ethnic-specific differences in the relationship between adipose tissue inflammation and insulin sensitivity2011In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 74, no 1, p. 51-59Article in journal (Refereed)
    Abstract [en]

    Objective  It is unclear whether there are differences in inflammatory gene expression between abdominal and gluteal subcutaneous adipose tissue (SAT), and between black and white women. We therefore tested the hypotheses that SAT inflammatory gene expression is greater in the abdominal compared to the gluteal depot, and SAT inflammatory gene expression is associated with differential insulin sensitivity (S(I) ) in black and white women.

    Design and methods  S(I) (frequently sampled intravenous glucose tolerance test) and abdominal SAT and gluteal SAT gene expression levels of 13 inflammatory genes were measured in normal-weight (BMI 18-25 kg/m(2) ) and obese (BMI >30 kg/m(2) ) black (n = 30) and white (n = 26) South African women.

    Results  Black women had higher abdominal and gluteal SAT expression of CCL2, CD68, TNF-α and CSF-1 compared to white women (P < 0·01). Multivariate analysis showed that inflammatory gene expression in the white women explained 56·8% of the variance in S(I) (P < 0·005), compared to 20·9% in black women (P = 0·30). Gluteal SAT had lower expression of adiponectin, but higher expression of inflammatory cytokines, macrophage markers and leptin than abdominal SAT depots (P < 0·05).

    Conclusions  Black South African women had higher inflammatory gene expression levels than white women; however, the relationship between AT inflammation and S(I) was stronger in white compared to black women. Further research is required to explore other factors affecting S(I) in black populations. Contrary to our original hypothesis, gluteal SAT had a greater inflammatory gene expression profile than abdominal SAT depots. The protective nature of gluteo-femoral fat therefore requires further investigation.

  • 17. Hou, Miao
    et al.
    Ji, Chenlin
    Wang, Jing
    Liu, Yanhua
    Sun, Bin
    Guo, Mei
    Buren, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Li, Xiaonan
    The effects of dietary fatty acid composition in the post-sucking period on metabolic alterations in adulthood: can omega 3 polyunsaturated fatty acids prevent adverse programming outcomes?2012In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 215, no 1, p. 119-127Article in journal (Refereed)
    Abstract [en]

    Early life nutrition is important in the regulation of metabolism in adulthood. We studied the effects of different fatty acid composition diets on adiposity measures, glucose tolerance, and peripheral glucocorticoid (GC) metabolism in overfed neonatal rats. Rat litters were adjusted to a litter size of three (small litters (SLs)) or ten (normal litters (NLs)) on postnatal day 3 to induce overfeeding or normal feeding respectively. After weaning, SL and NL rats were fed a omega 6 polyunsaturated fatty acid (PUFA) diet (14% calories as fat, soybean oil) or high-saturated fatty acid (high-fat; 31% calories as fat, lard) diet until postnatal week 16 respectively. SL rats were also divided into the third group fed a omega 3 PUFA diet (14% calories as fat, fish oil). A high-fat diet induced earlier and/or more pronounced weight gain, hyperphagia, glucose intolerance, and hyperlipidemia in SL rats compared with NL rats. In addition, a high-fat diet increased 11 beta-hsd1 (Hsd11b1) mRNA expression and activity in the retroperitoneal adipose tissue of both litter groups compared with standard chow counterparts, whereas high-fat feeding increased hepatic 11 beta-hsd1 mRNA expression and activity only in SL rats. SL and a high-fat diet exhibited significant interactions in both retroperitoneal adipose tissue and hepatic 11 beta-HSD1 activity. Dietary omega 3 PUFA offered protection against glucose intolerance and elevated GC exposure in the retroperitoneal adipose tissue and liver of SL rats. Taken together, the results suggest that dietary fatty acid composition in the post-sucking period may interact with neonatal feeding and codetermine metabolic alterations in adulthood. Journal of Endocrinology (2012) 215, 119-127

  • 18. Hou, Miao
    et al.
    Liu, Yanhua
    Zhu, Lijun
    Sun, Bin
    Guo, Mei
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Li, Xiaonan
    Neonatal overfeeding induced by small litter rearing causes altered glucocorticoid metabolism in rats2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 11, p. e25726-Article in journal (Refereed)
    Abstract [en]

    Elevated glucocorticoid (GC) activity may be involved in the development of the metabolic syndrome. Tissue GC exposure is determined by the tissue-specific GC-activating enzyme 11 beta-hydroxysteriod dehydrogenase type 1 (11 beta-HSD1) and the GC-inactivating enzyme 5 alpha-reductase type 1 (5 alpha R1), as well as 5 beta-reductase (5 beta R). Our aim was to study the effects of neonatal overfeeding induced by small litter rearing on the expression of GC-regulating enzymes in adipose tissue and/or liver and on obesity-related metabolic disturbances during development. Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litters, SL) or ten (normal litters, NL) on postnatal day 3 and then given standard chow from postnatal week 3 onward (W3). Small litter rearing induced obesity, hyperinsulinemia, and higher circulating corticosterone in adults. 11 beta-HSD1 expression and enzyme activity in retroperitoneal, but not in epididymal, adipose tissue increased with postnatal time and peaked at W5/W6 in both groups before declining. From W8, 11 beta-HSD1 expression and enzyme activity levels in retroperitoneal fat persisted at significantly higher levels in SL compared to NL rats. Hepatic 11 beta-HSD1 enzyme activity in SL rats was elevated from W3 to W16 compared to NL rats. Hepatic 5 alpha R1 and 5 beta R expression was higher in SL compared to NL rats after weaning until W6, whereupon expression decreased in the SL rats and remained similar to that in NL rats. In conclusion, small litter rearing in rats induced peripheral tissue-specific alterations in 11 beta-HSD1 expression and activity and 5 alpha R1 and 5 beta R expression during puberty, which could contribute to elevated tissue-specific GC exposure and aggravate the development of metabolic dysregulation in adults.

  • 19. Ji, Chenlin
    et al.
    Dai, Yanyan
    Jiang, Weiwei
    Liu, Juan
    Hou, Miao
    Wang, Junle
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Li, Xiaonan
    Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats2014In: Journal of Nutritional Biochemistry, ISSN 0955-2863, E-ISSN 1873-4847, Vol. 25, no 11, p. 1108-1116Article in journal (Refereed)
    Abstract [en]

    Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16 weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis. (C) 2014 Elsevier Inc. All rights reserved.

  • 20. Lindholm, Åsa
    et al.
    Blomquist, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Dahlbom, Ingrid
    Hansson, Tony
    Sundström Poromaa, Inger
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls.2011In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 26, no 6, p. 1478-85Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: BACKGROUND; Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue.

    METHODS: Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR.

    RESULTS: Overweight patients with PCOS had higher relative adipose tissue chemokine ligand 2 (P < 0.01), and its cognate receptor (P < 0.05), tumour necrosis factor-α (P < 0.001), interleukin (IL)-10 (P < 0.001) and IL-18 (P < 0.001) and the monocyte/macrophage markers CD14 (P < 0.01) and CD163 (P < 0.01) mRNA levels compared with lean women with PCOS. There were no differences between overweight patients with PCOS and overweight control subjects in this respect. Within the PCOS group, markers of adipose tissue inflammation correlated significantly with obesity-related metabolic disturbances, but when data were adjusted for age and BMI, most correlations were lost.

    CONCLUSIONS: Overweight, rather than the PCOS diagnosis per se, appears to be the main explanatory variable for elevated adipose tissue inflammation in patients with PCOS.

  • 21.
    Lindmark, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Jan W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo2006In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 65, no 3, p. 301-309Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). Design and methods Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age and body mass index. A hyperinsulinaemic, euglycaemic clamp was performed and cytokines and endocrine functions, including cortisol axis activity were assessed. Results Patients with diabetes were more insulin resistant than group C, and group P exhibited the highest degree of insulin resistance ( P = 0·01, P vs C). Tumour necrosis factor (TNF)-alpha levels were elevated in patients with diabetes ( P = 0·05) and group P had the highest levels of fasting serum cortisol ( P = 0·05), nonesterified fatty acids (NEFA; P = 0·06) and C-reactive protein (CRP; P = 0·01). Adiponectin levels were lower in the P group. In partial correlation analyses, significant associations were found: glycaemic level (HbA1c) with insulin resistance, TNF-alpha, CRP and basal and ACTH-stimulated cortisol levels, insulin resistance with plasma NEFA, TNF-alpha and stimulated cortisol levels. Conclusion Poor glycaemic control in patients with T2DM was associated with insulin resistance and with elevated TNF-alpha, CRP and basal as well as stimulated cortisol levels. Inflammatory mediators, e.g. TNF-alpha, may contribute to insulin resistance in hyperglycaemic patients with T2DM and this might be a partial explanation for glucotoxicity.

  • 22.
    Lundgren, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Buren, Jonas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Ruge, Toralph
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Myrnäs, Torbjörn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes.2004In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 89, no 6, p. 2989-2997Article in journal (Refereed)
  • 23.
    Lundgren, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindgren, P
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Myrnäs, Torbjörn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
    Ruge, Toralph
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Eriksson, Jan
    Sex- and depot-specific lipolysis regulation in human adipocytes: interplay between adrenergic stimulation and glucocorticoids2008In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 40, p. 854-860Article in journal (Refereed)
    Abstract [en]

    The purpose of this investigation was to explore interactions between adrenergic stimulation, glucocorticoids, and insulin on the lipolytic rate in isolated human adipocytes from subcutaneous and omental fat depots, and to address possible sex diff erences. Fat biopsies were obtained from 48 nondiabetic subjects undergoing elective abdominal surgery. Lipolysis rate was measured as glycerol release from isolated cells and proteins involved in lipolysis regulation were assessed by immunoblots. Fasting blood samples were obtained and metabolic and infl ammatory variables were analyzed. In women, the rate of 8-bromo-cAMP- and isoprenaline-stimulated lipolysis was ~ 2- and 1.5-fold higher, respectively, in subcutaneous compared to omental adipocytes, whereas there was no diff erence between the two depots in men. Dexamethasone treatment increased the ability of 8-bromo-cAMP to stimulate lipolysis in the subcutaneous depot in women, but had no consistent eff ects in fat cells from men. Protein kinase A, Perilipin A, and hormone sensitive lipase content in adipocytes was not aff ected by adipose depot, sex, or glucocorticoid treatment. In conclusion, catecholamine and glucocorticoid regulation of lipolysis in isolatedhuman adipocytes diff ers between adipose tissue depots and also between sexes. These findings may be of relevance for the interaction between endogenous stress hormones and adipose tissue function in visceral adiposity and the metabolic syndrome.

  • 24.
    Lundgren, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Burén, Jonas
    Lindgren, Peter
    Myrnäs, Torbjörn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ruge, Toralph
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Eriksson, Jan
    Sex differences in depot-specific lipolysis regulation in human adipocytes: interplay between adrenergic stimulation, glucocorticoids and insulinManuscript (Other (popular science, discussion, etc.))
  • 25.
    Renström, Frida
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Buren, Jonas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Insulin receptor substrates-1 and -2 are both depleted but via different mechanisms after down-regulation of glucose transport in rat adipocytes.2005In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 146, no 7, p. 3044-3051Article in journal (Refereed)
  • 26.
    Renström, Frida
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine. Medicin.
    Buren, Jonas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine. Medicin.
    Svensson, Maria
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine. Medicin.
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine. Medicin.
    Insulin resistance induced by high glucose and high insulin precedes insulin receptor substrate 1 protein depletion in human adipocytes.2007In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 56, no 2, p. 190-198Article in journal (Refereed)
  • 27.
    Renström, Frida
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Svensson, M K
    Eriksson, J W
    Factors in serum from type 2 diabetes patients can cause cellular insulin resistance.2009In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 41, no 10, p. 767-772Article in journal (Refereed)
    Abstract [en]

    This pilot study was aimed to investigate whether there are humoral factors in serum from type 2 diabetic subjects that, in addition to glucose, insulin and free fatty acids are able to induce or contribute to peripheral insulin resistance with respect to glucose transport. Isolated subcutaneous adipocytes from 11 type 2 diabetic subjects and 10 nondiabetic controls were incubated for 24-h in medium supplemented with 25 % serum from a control or a type 2 diabetic donor, in the presence of a low (5 mM) or a high (15 mM) glucose concentration, respectively. After the incubation period glucose uptake capacity was assessed. Serum from type 2 diabetic donors, compared to serum from controls, significantly reduced the maximal insulin eff ect to stimulate glucose uptake (approximately 40 %, p < 0.05) in adipocytes from control subjects, independent of surrounding glucose concentrations. Glucose uptake capacity in adipocytes isolated from type 2 diabetic subjects was similar regardless of culture condition. No significant alterations were found in cellular content of key proteins in the insulin signaling cascade (insulin receptor substrate-1 and -2, and glucose transporter 4) that could explain the impaired insulin-stimulated glucose transport in control adipocytes incubated with serum from type 2 diabetic donors. The present findings indicate the presence of biomolecules in the circulation of type 2 diabetic subjects, apart from glucose, insulin, and free fatty acids with the ability to induce peripheral insulin resistance. This further implies that even though normoglycemia is achieved other circulating factors can still negatively aff ect insulin sensitivity in type 2 diabetic patients.

  • 28.
    Sjödin, Anna
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Persson, Sarah
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Stigsson Claesson, Madeleine
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Burén, Jonas
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Motionärer och elit har samma koll på kosten2013In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, no 4, p. 35-37Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Elitspelare i innebandyns superliga har inte bättre kunskap än motionärer om vilka kostrekommendationer som gäller vid träning. Lägst kunskap har spelarna om kostens betydelse för uppladdningen. För att kunna prestera maximalt är det viktigt att kunna anpassa energi-, närings- och vätskeintag till sin idrott.

  • 29. Yu, Z W
    et al.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Enerbäck, S
    Nilsson, E
    Samuelsson, L
    Eriksson, J W
    Insulin can enhance GLUT4 gene expression in 3T3-F442A cells and this effect is mimicked by vanadate but counteracted by cAMP and high glucose--potential implications for insulin resistance.2001In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1535, no 2, p. 174-85Article in journal (Refereed)
    Abstract [en]

    It is well-established that high levels of cAMP or glucose can produce insulin resistance. The aim of this study was to characterize the interaction between these agents and insulin with respect to adipose tissue/muscle glucose transporter isoform (glucose transporter 4, GLUT4) gene regulation in cultured 3T3-F442A adipocytes and to further elucidate the GLUT4-related mechanisms in insulin resistance. Insulin (10(4) microU/ml) treatment for 16 h clearly increased GLUT4 mRNA level in cells cultured in medium containing 5.6 mM glucose but not in cells cultured in medium with high glucose (25 mM). 8-Bromo-cAMP (1 or 4 mM) or N(6)-monobutyryl cAMP, a hydrolyzable and a non-hydrolyzable cAMP analog, respectively, markedly decreased the GLUT4 mRNA level irrespective of glucose concentrations. In addition, these cAMP analogs also inhibited the upregulating effect of insulin on GLUT4 mRNA level. Interestingly, the tyrosine phosphatase inhibitor vanadate (1-50 microM) clearly increased GLUT4 mRNA level in a time- and concentration-dependent manner. Furthermore, cAMP-induced inhibition of the insulin effect was also prevented by vanadate. In parallel to the effects on GLUT4 gene expression, both insulin, vanadate and cAMP produced similar changes in cellular GLUT4 protein content and cAMP impaired the effect of insulin to stimulate (14)C-deoxyglucose uptake. In contrast, insulin, vanadate or cAMP did not alter insulin receptor (IR) mRNA or the cellular content of IR protein. In conclusion: (1) Both insulin and vanadate elicit a stimulating effect on GLUT4 gene expression in 3T3-F442A cells, but a prerequisite is that the surrounding glucose concentration is low. (2) Cyclic AMP impairs the insulin effect on GLUT4 gene expression, but this is prevented by vanadate, probably by enhancing the tyrosine phosphorylation of signalling peptides and/or transcription factors. (3) IR gene and protein expression is not altered by insulin, vanadate or cAMP in this cell type. (4) The changes in GLUT4 gene expression produced by cAMP or vanadate are accompanied by similar alterations in GLUT4 protein expression and glucose uptake, suggesting a role of GLUT4 gene expression for the long-term regulation of cellular insulin action on glucose transport.

  • 30. Zhu, Lijun
    et al.
    Hou, Miao
    Sun, Bin
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhang, Li
    Yi, Jun
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Li, Xiaonan
    Testosterone Stimulates Adipose Tissue 11 beta-Hydroxysteroid Dehydrogenase Type 1 Expression in a Depot-Specific Manner in Children2010In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 7, p. 3300-3308Article in journal (Refereed)
    Abstract [en]

    Context: Activation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue results in the production of excess tissue glucocorticoids and the induction of adiposity and visceral obesity in particular. Androgens may affect body fat distribution by regulating the local metabolism of cortisol.

    Objective: Our objective was to study 11beta-HSD1 mRNA expression in abdominal sc and omental (om) adipose tissue in children after in vitro testosterone and cortisol treatment.

    Subjects and Methods: Paired fat biopsies (sc and om) were obtained from 19 boys (age 6-14 yr, body mass index 14.6-25.3 kg/m(2), BMI SD score SDS -1.6-3.1) undergoing open abdominal surgery. Pieces of adipose tissue were incubated with testosterone, cortisol, or both hormones for 24 h, whereupon mRNA expression of 11beta-HSD1 and hexose-6-phosphate dehydrogenase (H6PDH) were measured by real-time PCR, and 11beta-HSD1 enzyme activity was determined.

    Results: Testosterone treatment up-regulated 11beta-HSD1 mRNA expression compared with control incubations in the absence of testosterone (P < 0.05) in om adipose tissue. Testosterone and cortisol both increased 11beta-HSD1 mRNA expression in om but not sc adipose tissue in a depot-specific manner by 2.5- and 2.9-fold, respectively (P < 0.001). However, there was no synergistic effect of the two hormones. 11beta-HSD1 enzyme activity correlated positively to mRNA expression (r = 0.610; P = 0.001). Adipose tissue mRNA expression of H6PDH was affected in a similar fashion to 11beta-HSD1 after hormonal treatment.

    Conclusions: Testosterone and cortisol stimulated 11beta-HSD1 and H6PDH mRNA expression and 11beta-HSD1 activity in om but not in sc adipose tissue. This suggests that these hormones may contribute to fat distribution and accumulation during childhood.

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