[Regulation of glucose metabolism by insulin: dual role of protein kinase C].
The role that protein kinase C (PKC) may play on insulin regulation of glucose metabolism was investigated in rat adipocytes and Zajdela hepatoma cultured (ZHC) cells which are two cell types highly responsive to insulin. In rat adipocytes, 4 beta-phorbol 12 beta-myristate, 13 alpha-acetate (PMA, 0.1-1,000 ng/ml), a potent tumor promoter acting as a substitute for diacylglycerol which directly activates PKC, stimulated basal 2-deoxyglucose (2-DG) transport in a time- and dose-dependent manner, but decreased the activation of this process elicited by submaximal concentrations of insulin. PMA (0.1-1,000 ng/ml) also stimulated basal lipogenesis from [3-3H] glucose in a dose-dependent manner. Maximal PMA and insulin effects on both processes were not additive. The specificity of the insulin-like effects of PMA was assessed by the finding that 4 beta-phorbol 12, 13 dibutyrate (PDBu), mezerein, 1-oleyl-2-acetyl glycerol (OAG) and 1, 2 diolein, know as PKC activators, also markedly stimulated glucose metabolism whereas 4 alpha-phorbol 12, 13 didecanoate (4 alpha-PDD) and 4 beta-phorbol 13-monoacetate, shown not to activate PKC, were ineffective. PMA and insulin biological effects exhibited several similarities: both agents stimulated glucose transport and lipogenesis in a calcium-dependent manner, both activated glucose transport through an energy-requiring process, and the effects of both were markedly decreased by mellitin, a PKC inhibitor. Finally, fat cells made PKC-deficient by a chronic treatment with PMA exhibited a marked decrease in insulin responsiveness for stimulation of glucose transport and lipogenesis, with no change in either the hormone sensitivity or the insulin receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
Cherqui
G
G
Laboratoire de Biochimie, INSERM U 181, Faculté de Médecine Saint-Antoine, Paris.
Caron
M
M
Wicek
D
D
Capeau
J
J
Lascols
O
O
Picard
J
J
D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004140:Dinitrophenols; D007328:Insulin; D008555:Melitten; D003847:Deoxyglucose; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium
Régulation du métabolisme glucidique par l'insuline: rôle ambivalent de la protéine kinase C.