We have previously suggested that insulin effects on 2-deoxyglucose (2-DOG) uptake in BC3H-1 myocytes are due to increases in de novo phospholipid synthesis, diacylglycerol generation, and protein kinase C activation. To test this hypothesis further, we examined the effects of phenylephrine, an agonist that increases diacylglycerol and protein kinase C activity through phospholipase C activation. As evidence for phospholipase activation in BC3H-1 myocytes, we found that phenylephrine increased 7) acute 32PO4 incorporation into phosphatidic acid and phosphatidylinositol, 2) generation of [3H]inositol phosphates from prelabeled [3H]inositol phospholipids, 3) cytosolic Ca2+, and 4) membrane-bound protein kinase C. Phenylephrine also provoked dose-related increases in [3H]-DOG uptake that were similar in magnitude and time course to those induced by insulin. As with insulin, phenylephrine effects on 2-DOG uptake were not apparent in myocytes that were maximally stimulated with 12-O- tetradecanoylphorbol-13-acetate, a diacylglycerol analogue that activates protein kinase C. These findings support our hypothesis that diacylglycerol generation and protein kinase C activation may be important in the stimulation of glucose uptake by agents such as phenylephrine and insulin that activate the phosphoinositide cycle.
Further Evidence Implicating Diacylglycerol Generation and Protein Kinase C Activation in Agonist-Induced Increases in Glucose Uptake: Insulin-Like Effects of Phenylephrine in BC3H-1 Myocytes
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R V Farese, N Rosic, M Standaert, J Babischkin, D R Cooper, J S Davis, R J Pollet; Further Evidence Implicating Diacylglycerol Generation and Protein Kinase C Activation in Agonist-Induced Increases in Glucose Uptake: Insulin-Like Effects of Phenylephrine in BC3H-1 Myocytes. Diabetes 1 September 1986; 35 (9): 951–957. https://doi.org/10.2337/diab.35.9.951
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