Glucocorticoid-induced insulin resistance associates with activation of protein kinase C isoforms.

Abstract	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.
Authors	K Kajita, T Ishizuka, A Miura, Y Kanoh, M Ishizawa, M Kimura, N Muto, K Yasuda
Journal	Cellular signalling (Cell Signal) Vol. 13 Issue 3 Pg. 169-75 (Mar 2001) ISSN: 0898-6568 [Print] England
PMID	11282455 (Publication Type: Journal Article)
Chemical References	Enzyme Inhibitors Glucocorticoids Insulin Insulin Antagonists Isoenzymes Dexamethasone Deoxyglucose Prednisolone Protein Kinase C Corticosterone
Topics	Adipocytes (diagnostic imaging, drug effects) Animals Biological Transport (drug effects, immunology) Cell Membrane (drug effects, immunology) Cell Separation Cells, Cultured Corticosterone (pharmacology) Cytosol (drug effects, immunology) Deoxyglucose (pharmacokinetics) Dexamethasone (pharmacology) Electrophoresis, Polyacrylamide Gel Enzyme Activation Enzyme Inhibitors (pharmacology) Glucocorticoids (pharmacology) Insulin (pharmacology) Insulin Antagonists (pharmacology) Insulin Resistance Isoenzymes (immunology, metabolism) Male Precipitin Tests Prednisolone (pharmacology) Protein Kinase C (metabolism) Radionuclide Imaging Rats Rats, Wistar Time Factors

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