JNK and IKKβ phosphorylation is reduced by glucocorticoids in adipose tissue from insulin-resistant rats

How much we know about the attenuation of insulin signaling in the adipose tissue caused by glucocorticoid treatment?

“…In accordance, the ability of insulin to inhibit 8-bromo cAMP-stimulated glycerol release in adipocytes is significantly reduced in rats treated with dexamethasone for 11 consecutive days [14] . Furthermore, rats treated with dexamethasone [15] and corticosterone [10] for 5 or 10 consecutive days, respectively, also develop augmented lipolysis rate preferentially under basal condition. This dual effect of GCs on visceral fat (induction of adipogenesis and lipolysis) corroborates to the expansion of abdominal fat and to the increase of hepatic flux of lipids that may lead to hepatosteatosis [10,17] .…”

“…GCs modulate several processes in the adipose tissue such as adipocyte differentiation/adipogenesis [9][10][11][12][13] , and exert both anabolic (e.g., lipogenesis) and catabolic (e.g., lipolysis) [10][11][12][13][14][15][16] functions, depending on the fat depot evaluated and stage of adipocyte differentiation/maturation. It is consensually accepted that GCs promote adipogenesis and/or lipogenesis (visceral adipose tissue) and lipolysis (subcutaneous adipose tissues), which correspond with clinical features of abdominal obesity and limited subcutaneous fat on the extremities in patients with Cushing's syndrome [4] .…”

“…It is consensually accepted that GCs promote adipogenesis and/or lipogenesis (visceral adipose tissue) and lipolysis (subcutaneous adipose tissues), which correspond with clinical features of abdominal obesity and limited subcutaneous fat on the extremities in patients with Cushing's syndrome [4] . GCs also promote lipolysis in differentiated adipocytes and/or adipose tissue fragments explanted from visceral depots [10,14,15] . In accordance, the ability of insulin to inhibit 8-bromo cAMP-stimulated glycerol release in adipocytes is significantly reduced in rats treated with dexamethasone for 11 consecutive days [14] .…”

“…Rats treated with GCs exhibit reduced insulin response in the epididymal fat/adipocytes that is associated with diminished insulin receptor substrate (IRS)-1 and IRS-2 Tyr phosphorylation, decreased IRS-1 and IRS-2 association with the phosphatidylinositol 3-kinase (PI3K), decreased protein kinase B (PKB) Ser and Thr phosphorylation, and reduced atypical protein kinase C (PKC)ζ phosphorylation [10,14,15,18] . These rats also exhibit increased mRNA and protein content of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in the epididymal tissue [10] .…”

“…The exact mechanisms by which GCs attenuate the main insulin signaling components (e.g., IRSs and PKB proteins) are not well established. It was recently demonstrated that rats treated with dexamethasone for 5 consecutive days exhibit reduced PKB Ser phosphorylation in the epididymal fat after an oral bolus of glucose, indicating that a physiological peak of insulin does not result in proper insulin cascade activation [15] .…”