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Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects
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2003 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 166, no 2, 359-367Article in journal (Refereed) Published
Abstract [en]

Background/aim: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL).

Subjects and methods: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin.

Results: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0±0.4 vs 2.0±0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by ∼35–55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR.

Conclusion: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.

Keyword [en]
Type 2 diabetes, Adipose tissue, Lipoprotein lipase, Insulin resistance, Glucose uptake, Triglycerides, Free fatty acids, Postprandial
National Category
Endocrinology and Diabetes
URN: urn:nbn:se:umu:diva-3934DOI: 10.1016/S0021-9150(02)00366-0OAI: diva2:142847
Available from2002-12-06 Created:2002-12-06 Last updated:2012-05-16Bibliographically approved
In thesis
1. Glucose and lipid metabolism in insulin resistance
Open this publication in new window or tab >>Glucose and lipid metabolism in insulin resistance : an experimental study in fat cells
2003 (English)Doctoral 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


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.

Publisher, range
Umeå: Folkhälsa och klinisk medicin, 2003. 63 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 817
Public health, adipocyte, insulin resistance, type 2 diabetes, insulin signalling, glucose uptake, insulin, glucose, dexamethasone, insulin receptor substrate, protein kinase B, GLUT4, lipoprotein lipase, Folkhälsomedicin
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
urn:nbn:se:umu:diva-26 (URN)91-7305-359-7 (ISBN)
Public defence
2002-12-06, Umeå, 13:00
Available from2002-12-06 Created:2002-12-06 Last updated:2010-06-17Bibliographically approved

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Eriksson, Jan. W.Burén, JonasSvensson, MariaOlivecrona, ThomasOlivecrona, Gunilla
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