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Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes.
Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Kirurgi.
Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Kirurgi.
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2004 (Engelska)Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 89, nr 6, s. 2989-2997Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2004. Vol. 89, nr 6, s. 2989-2997
Nyckelord [en]
Adipocytes/cytology/*drug effects/*metabolism, Adolescent, Adult, Aged, Aged; 80 and over, Biological Transport/drug effects, Carbon Radioisotopes/diagnostic use, Cells; Cultured, Dexamethasone/*pharmacology, Female, Glucocorticoids/*pharmacology, Glucose/pharmacokinetics, Glucose Transporter Type 4, Humans, Insulin/metabolism, Male, Middle Aged, Monosaccharide Transport Proteins/metabolism, Muscle Proteins, Omentum/*cytology/metabolism, Signal Transduction/drug effects, Subcutaneous Tissue/metabolism
Identifikatorer
URN: urn:nbn:se:umu:diva-12997DOI: 10.1210/jc.2003-031157PubMedID: 15181089OAI: oai:DiVA.org:umu-12997DiVA, id: diva2:152668
Tillgänglig från: 2007-12-05 Skapad: 2007-12-05 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Interplay between hormones, nutrients and adipose depots in the regulation of insulin sensitivity: an experimental study in rat and human adipocytes
Öppna denna publikation i ny flik eller fönster >>Interplay between hormones, nutrients and adipose depots in the regulation of insulin sensitivity: an experimental study in rat and human adipocytes
2006 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Obesity and specifically central obesity is related to insulin resistance, type 2 diabetes and other components of the so-called metabolic syndrome. The aim of this study was to elucidate the interplay between hormones, nutrients and adipose depots in normal and insulin-resistant fat cell metabolism.

High levels of free fatty acids (FFAs) induce insulin resistance in muscle and liver in vivo. In the present study, rat adipocytes were treated with high physiological levels of oleic or palmitic acid in vitro for 4-24 h. This treatment had no effect on basal or insulin-stimulated glucose uptake capacity in these cells, neither did it affect the levels of the insulin signalling proteins; insulin receptor substrate (IRS)-1 or –2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B (PKB) or glucose transporter (GLUT) 4, or the regulation of lipolysis rate.

Visceral adiposity is considered to be more harmful than peripheral adiposity with respect to metabolic and cardiovascular complications. In adipose biopsies from subjects undergoing abdominal surgery, we found that glucose uptake capacity was elevated in omental as compared to subcutaneous adipocytes. The sensitivity (EC50) or maximum relative response to insulin, measured as % of basal, did however not differ between the depots. In women, subcutaneous adipocytes displayed a higher lipolysis rate following cAMP-stimulation than omental adipocytes, whereas there was a tendency towards the opposite in adipocytes from men. No differences were found between depots or sexes in the ability of insulin to inhibit lipolysis or in the levels of the lipolysis regulating proteins, i.e. protein kinase A (PKA), hormone sensitive lipase (HSL) and perilipin.

Glucocorticoids, e.g. cortisol, exert pronounced insulin-antagonistic effects and are associated with redistribution of fat from peripheral to central fat depots in humans. Treatment of human subcutaneous and omental adipocytes in vitro, with the cortisol analogue dexamethasone, resulted in a dose dependent down-regulation of basal and insulin-stimulated glucose uptake capacity in omental, but not in subcutaneous cells. Concomitantly, the levels of IRS-1 and PKB were decreased only in omental adipocytes after dexamethasone treatment. The relative effect of insulin to stimulate glucose uptake was however not altered by dexamethasone treatment. The cAMP-stimulated lipolysis rate was elevated by dexamethasone treatment in cells from the subcutaneous depot in women and tended to be elevated in omental cells from men. No alterations however, were seen in the levels of the assessed lipolysis regulating proteins.

Subcutaneous as well as omental fat cell size correlated negatively to insulin action in subcutaneous fat cells in vitro after adjusting for age, sex and body fat parameters in non-diabetic, but not in type 2 diabetic, subjects. Large subcutaneous fat cell size was strongly related to plasma leptin levels in non-diabetic and in type 2 diabetic subjects.

We conclude that 1) adipocytes seem to be less vulnerable to elevated levels of fatty acids than muscle and liver cells, 2) the interactions between glucocorticoids and insulin in the regulation of glucose uptake differ between adipose depots, 3) depot specific hormonal lipolysis regulation differs between sexes and 4) fat cell size is related to insulin action in subcutaneous fat cells and to circulating levels of leptin.

Ort, förlag, år, upplaga, sidor
Umeå: Folkhälsa och klinisk medicin, 2006. s. 59
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 996
Nyckelord
adipose tissue, cAMP, glucocorticoids, glucose, insulin, insulin resistance, lipolysis, subcutaneous fat, type 2 diabetes, visceral fat
Nationell ämneskategori
Klinisk vetenskap
Identifikatorer
urn:nbn:se:umu:diva-677 (URN)91-7305-987-0 (ISBN)
Disputation
2006-02-24, Sal B, plan 9, 1D, NUS, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2006-01-30 Skapad: 2006-01-30 Senast uppdaterad: 2009-10-12Bibliografiskt granskad

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Buren, JonasRuge, ToralphEriksson, Jan

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