Effect of dexamethasone and prednisolone on insulin-induced activation of protein kinase C in rat adipocytes and soleus muscles.
We examined the effect of glucocorticoids on [3H]2-deoxyglucose ([3H]2-DOG) uptake, [125I]insulin binding, tyrosine kinase activity, and protein kinase C (PKC) activity in rat adipocytes and soleus muscles. In adipocytes, insulin-stimulated [3H]2-DOG uptake was decreased by prior 60-minute treatment with dexamethasone (DEX) or prednisolone (PSL), whereas [125I]insulin binding, insulin (INS) receptor autophosphorylation, and tyrosine kinase activity, as measured using exogenous substrate of poly(Glu80-Tyr20), were not significantly changed. Cytosolic PKC activity decreased and membrane-associated PKC activity increased during a 60-minute treatment of adipocytes and soleus muscles with DEX or PSL, indicating that both DEX and PSL stimulate the translocation and activation of PKC. However, pretreatment of adipocytes and soleus muscles with glucocorticoids resulted in reduced INS-stimulated translocation of PKC from cytosol to membrane. INS-induced decreases in cytosolic PKC activity (50% +/- 7% v 10% +/- 8% and 20% +/- 7%, P < .05 to .01, for nonpretreated [control], DEX pretreated, and PSL pretreated cells) and increases in membrane PKC (100% +/- 10% v 50% +/- 9% and 20% +/- 9%, P < .01, for control, DEX pretreated, and PSL pretreated cells) were larger in nonpretreated adipocytes than in adipocytes pretreated with glucocorticoids. These results raise the possibility that glucocorticoids, namely, DEX and PSL, stimulate the translocation and subsequent degradative downregulation of PKC, and that this may be pertinent to their inhibitory effects on INS-stimulated glucose transport.
Ishizuka
T
T
Third Department of Internal Medicine, Gifu University School of Medicine, Japan.
Yamamoto
M
M
Nagashima
T
T
Kajita
K
K
Taniguchi
O
O
Yasuda
K
K
Miura
K
K
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D007328:Insulin; D003907:Dexamethasone; D003847:Deoxyglucose; D011239:Prednisolone; D011493:Protein Kinase C