title: Insulin stimulation of glucose metabolism in rat adipocytes: possible implication of protein kinase C.
abstract: The hypothesis that insulin stimulation of glucose and lipid metabolism in rat adipocytes may involve the activation of protein kinase C was evaluated. 4 beta-Phorbol 12 beta-myristate, 13 alpha-acetate (PMA, 0.1-1000 ng/ml), a potent tumor promoter acting as a substitute for diacylglycerol to activate protein kinase C, stimulated 2-deoxyglucose transport in a time- and dose-dependent manner, without affecting passive glucose diffusion. PMA (0.1-1000 ng/ml) also elicited a dose-dependent activation of lipogenesis from [3-3H] glucose. Maximal PMA effects (100 ng/ml) on both processes were 60% of insulin maximal effects. In contrast, PMA (1-1000 ng/ml) failed to mimic the ability of insulin to stimulate lipogenesis from [3H]acetate. 4 beta-Phorbol 12,13 dibutyrate, mezerein, 1-oleyl-2-acetyl-glycerol, 1,2 diolein, known as protein kinase C activators, also markedly stimulated glucose metabolism whereas 4 alpha-phorbol 12,13 didecanoate and 4 beta-phorbol 13-monoacetate, shown not to activate protein kinase C, were ineffective. Mellitin, a cytotoxin-inhibiting protein kinase C, markedly decreased both PMA and insulin stimulation of glucose metabolism. PMA decreased insulin submaximal effects on 2-deoxyglucose transport without inhibiting insulin binding. Maximal PMA and insulin effects on 2-deoxyglucose transport and lipogenesis from [3-3H]glucose were not additive. Both PMA and insulin activated each metabolic process in a calcium-dependent manner. PMA, like insulin, no longer stimulated 2-deoxyglucose transport in fat cells treated with 2,4-dinitrophenol. These data show that PMA exhibited specific insulin-like properties on glucose metabolism in fat cells, without any effect on lipid synthesis from acetate. They indicate that PMA and insulin bioeffects may share a common step implicating a calcium- and energy-dependent process, distal to the initial insulin binding event. Our results suggest that protein kinase C may play a role in insulin regulation of glucose metabolism.
mesh_terms: D019297:2,4-Dinitrophenol; D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000085:Acetates; D004140:Dinitrophenols; D007328:Insulin; D008055:Lipids; D003847:Deoxyglucose; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D019297:2,4-Dinitrophenol; D019342:Acetic Acid