Short-and long-term glucocorticoid treatment enhances insulin signalling in human subcutaneous adipose tissue

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Gathercole, LL ; Morgan, SA ; Bujalska, IJ ; Stewart, PM ; Tomlinson, JW (2011)
  • Publisher: Nature Publishing Group
  • Journal: Nutrition & Diabetes, volume 1, issue 1, page e3 (eissn: 2044-4052)
  • Related identifiers: doi: 10.1038/nutd.2010.3, pmc: PMC3302128
  • Subject: Original Article | cortisol | adipocyte | insulin signalling | glucocorticoids | obesity

Background: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's syndrome) is characterized by increased adiposity and insulin resistance. Although GCs cause global insulin resistance in vivo, we have previously shown that GCs are able to augment insulin action in human adipose tissue, contrasting with their action in skeletal muscle. Cushing's syndrome develops following chronic GC exposure and, in addition, is a state of hyperinsulinemia. Objectives: We have therefore compared the impact of short- (24 h) and long-term (7 days) GC administration on insulin signalling in differentiated human adipocytes in the presence of low or high concentrations of insulin. Results: Both short- (24 h) and long-term (7 days) treatment of chub-s7 cells with dexamethasone (Dex) (0.5 μ) increased insulin-stimulated pTyr612IRS1 and pSer473akt/PKB, consistent with insulin sensitization. Chronic high-dose insulin treatment induced insulin resistance in chub-s7 cells. However, treatment with both high-dose insulin and Dex in combination still caused insulin sensitization. Conclusions: In this human subcutaneous adipocyte cell line, prolonged GC exposure, even in the presence of high insulin concentrations, is able to cause insulin sensitization. We suggest that this is an important mechanism driving adipogenesis and contributes to the obese phenotype of patients with Cushing's syndrome.
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