Ectopic expression of protein kinase CβII, -δ, and -ε, but not -βI or -ζ, provide for insulin stimulation of glucose uptake in NIH-3T3 cells
Ectopic expression of protein kinase CβII, -δ, and -ε, but not -βI or -ζ, provide for insulin stimulation of glucose uptake in NIH-3T3 cells
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DOI：
10.1006/abbi.1999.1472
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发表时间：
1999-12-01
影响因子：
3.9
通讯作者：
Mischak, H
中科院分区：
文献类型：
--
作者：
Cooper, DR;Watson, JE;Mischak, H
Insulin regulates a diverse array of signaling pathways involved in the control of growth, differentiation, proliferation, and metabolism. Insulin increases in glucose uptake via a protein kinase C-dependent pathway in target tissues such as fat and muscle are well documented. Insulin-regulated events, however, occur in all cells, The utilization of glucose as a preferred energy source is a ubiquitous event in eukaryotic cells. In NIH-3T3 fibroblasts, insulin treatment increased levels of the cPKC and nPKC activator, diacylglycerol. Insulin-responsive 2-[H-3]deoxyglucose uptake was stimulated in a dose-dependent manner. The overexpression of protein kinase C (PKC)beta I, -beta II, -delta, -epsilon, and -zeta was used to investigate the specificity of PKC isozymes for insulin-sensitive glucose uptake. The stable overexpression of PKC beta II, -delta, and -epsilon resulted in increases in insulin-stimulated 2-[H-3]deoxyglucose uptake compared to vector control cells, while basal 2-deoxyglucose uptake levels were not elevated. Overexpression of PKC beta I and PKC zeta isozymes had no further effect on basal or insulin-stimulated 2-deoxyglucose uptake. The PKC-specific inhibitor, CGP41251, blocked insulin effects on 2-deoxyglucose uptake but not its effects on tyrosine phosphorylation of cellular substrates. Insulin-stimulated 3-O-methylglucose uptake was also greater in cells overexpressing PKC beta II,-delta, and -epsilon, compared to control cells. The increased responsiveness was not accompanied by conversion of 3T3 cells to the adipocyte phenotype or the increased expression of insulin receptors or glucose transporters (GLUT1-type). Insulin-stimulated recruitment of GLUT1 to plasma membranes of cells overexpressing PKC beta II, -delta, and -epsilon, was greater than that in control cells. The data suggest that more than one PKC isozyme is involved in insulin signaling pathways in fibroblasts, resulting in increased GLUT1 transporter recruitment to cell membranes. (C) 1999 Academic Press.
