Inhibition of PKCbeta improves glucocorticoid-induced insulin resistance in rat adipocytes.
Pretreatment with glucocorticoids for 60 min depressed insulin-stimulated uptake of 2-[3H] deoxyglucose (2-DOG), an effect that neither cycloheximide, an inhibitor of protein synthesis, nor RU38486, a glucocorticoid receptor antagonist, could restore. Preincubation with conventional PKC inhibitors restored dexamethasone-induced insulin resistance. We also examined the dexamethasone-mediated inhibitory effect on insulin-induced 2-DOG uptake in adipocytes overexpressed with wild-type and dominant negative forms of PKCbeta. The dexamethasone-mediated inhibitory effect on insulin-induced 2-DOG uptake was abrogated in adipocytes overexpressed with dominant-negative PKCbeta. These results indicate that PKCbeta may play an important role in glucocorticoid-induced insulin resistance.
Kawai
Yasunori
Y
The Third Department of Internal Medicine, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500, Japan.
Ishizuka
Tatsuo
T
Kajita
Kazuo
K
Miura
Atsushi
A
Ishizawa
Masayoshi
M
Natsume
Yoshiyuki
Y
Uno
Yoshihiro
Y
Morita
Hiroyuki
H
Yasuda
Keigo
K
D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005799:Genes, Dominant; D005938:Glucocorticoids / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013997:Time Factors; D014162:Transfection
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D006727:Hormone Antagonists; D011500:Protein Synthesis Inhibitors; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D003513:Cycloheximide; D011493:Protein Kinase C; D064546:Protein Kinase C beta