Glucocorticoid-induced insulin resistance associates with activation of protein kinase C isoforms.
We studied glucocorticoid-induced insulin resistance and possible role of protein kinase C (PKC). Pretreatment with dexamethasone, prednisolone and corticosterone for 60 min decreased insulin-induced [3H] 2-deoxyglucose (DOG) uptake in isolated rat adipocytes. Preincubation with Go6976, LY379196 or myristoylated PKC pseudosubstrate, conventional PKC inhibitor, but not cycloheximide or RU38486, recovered dexamethasone-induced insulin resistance. Dexamethasone activated immunoprecipitates with anti-PKC alpha, beta, and zeta antibodies. PKC zeta activity in adipocytes increased to 163%, and 264% from basal level (100%) with dexamethasone and insulin treatment, respectively. Dexamethasone provoked redistribution of both PKC beta and zeta from the cytosol to the membrane. These results indicate that dexamethasone activates both conventional and atypical PKC. However, conventional PKC is more important in glucocorticoid-induced insulin resistance.
Kajita
K
K
The Third Department of Internal Medicine, Gifu University School of Medicine, Tsukasa-machi 40, 500-8705, Gifu, Japan.
Ishizuka
T
T
Miura
A
A
Kanoh
Y
Y
Ishizawa
M
M
Kimura
M
M
Muto
N
N
Yasuda
K
K
D017667:Adipocytes / Q000000981:diagnostic imaging* / Q000187:drug effects*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects* / Q000276:immunology; D002462:Cell Membrane / Q000187:drug effects* / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000276:immunology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology; D007333:Insulin Resistance; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D008297:Male; D011233:Precipitin Tests; D011239:Prednisolone / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007328:Insulin; D007329:Insulin Antagonists; D007527:Isoenzymes; D003907:Dexamethasone; D003847:Deoxyglucose; D011239:Prednisolone; D011493:Protein Kinase C; D003345:Corticosterone