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.
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 acute 32PO4 incorporation into phosphatidic acid and phosphatidylinositol, generation of [3H]inositol phosphates from prelabeled [3H]inositol phospholipids, cytosolic Ca2+, and membrane-bound protein kinase C. Phenylephrine also provoked dose-related increases in [3H]2-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.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004075:Diglycerides / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000096:biosynthesis*; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D003837:Deoxy Sugars; D004075:Diglycerides; D005989:Glycerides; D007328:Insulin; D010743:Phospholipids; D010656:Phenylephrine; D007294:Inositol; D003847:Deoxyglucose; D011493:Protein Kinase C; D002118:Calcium