Dominant negative protein kinase Cbeta improves 1alpha, 25-dihydroxy vitamin D3-induced insulin resistance.
1alpha,25-Dihydroxy vitamin D3 (1,25D3) activates conventional PKC and may subsequently lead to insulin resistance. Previous studies from our laboratory have shown that pretreatment with 10 nM-10 microM 1,25D3 dose-responsively suppressed insulin-induced glucose. To assess PKC(beta)-mediated inhibition of insulin-induced glucose uptake in rat adipocytes, we preincubated with Go6976 and LY379196, conventional PKC inhibitors, and found they abolished the 1,25D3-mediated inhibitory effect on insulin-induced 2-deoxyglucose (DOG) uptake. Moreover, the inhibitory effect of 1,25D3 on insulin-induced DOG uptake was abrogated in adipocytes overexpressed with dominant negative PKC(beta), but not in those overexpressed with wild type PKC(beta). These results suggest that 1,25D3 reduces insulin-induced glucose uptake via activation of PKC(beta) in rat adipocytes.
Natsume
Yoshiyuki
Y
Third Department of Internal Medicine, Gifu University School of Medicine, Tsukasamachi, Gifu, Japan.
Ishizuka
Tatsuo
T
Yamamoto
Yoritsuna
Y
Miura
Atsushi
A
Kajita
Kazuo
K
Ishizawa
Masayoshi
M
Kawai
Yasunori
Y
Huang
Yannan
Y
Morita
Hiroyuki
H
Uno
Yoshihiro
Y
Yasuda
Keigo
K
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D005799:Genes, Dominant; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D064546:Protein Kinase C beta; D051381:Rats; D013552:Swine; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007328:Insulin; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D003847:Deoxyglucose; D011493:Protein Kinase C; D064546:Protein Kinase C beta