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Insulin Stimulation of Glucose Metabolism in Rat Adipocytes: Possible Implication of Protein Kinase C^*

Laboratoire de Biochimie, INSERM U 181, Faculté de Médecine Saint-Antoine 75571 Paris Cédex 12, France

Address correspondence and requests for reprints to: Jacques Picard, Laboratoire de Biochimie, INSERM U 181, Faculté de Médecine Saint-Antoine, 27, rue Chaligny, 75571 Paris Cédex 12, France.

Abstract

The hypothesis that insulin stimulation of glucose and lipid metabolism in rat adipocytes may involve the activation of protein kinase C was evaluated.

4β-Phorbol 12β-myristate,13-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.

4β-Phorbol 12,13 dibutyrate, mezerein, l-oleyl-2-acetyl-glycerol, 1,2 diolein, known as protein kinase C activators, also markedly stimulated glucose metabolism whereas 4-phorbol 12,13 didecanoate and 4β-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. (Endocrinology 118: 1759–1769, 1986)

Footnotes

^* This work was supported by Grant U181 from the INSERM and by Grant UA0527 from the CNRS.

Received July 8, 1985.

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