Insulin stimulates a novel GTPase activity in human platelets.
Insulin stimulated the activity of a high-affinity GTPase activity in human platelet membranes some 62% over that of the basal activity. Half-maximal stimulation (Ka) was achieved with 3.1 nM insulin. The Km for GTP of the insulin-stimulated GTPase was 0.6 microM GTP. Treatment of isolated platelet membranes with cholera toxin, but not pertussis toxin, blocked insulin's ability to stimulate GTPase activity. Cholera toxin acted as a more potent inhibitor of the insulin-stimulated GTPase activity than that of the GTPase activity of the stimulatory guanine nucleotide regulatory protein, Gs, as monitored by stimulation using prostaglandin E1 (PGE1). Mixed ligand experiments showed that insulin stimulated GTPase activity in an additive fashion to GTPase activity stimulated by PGE1, due to Gs; by adrenaline (+ propranolol), due to the inhibitory guanine nucleotide regulatory protein, G1 and by vasopressin, which stimulates the putative 'Gp', a G-protein suggested to control the stimulation of inositol phospholipid metabolism. Insulin thus appears to stimulate a novel high-affinity GTPase activity in human platelet membranes. This may reflect the functioning of the putative Gins, a guanine nucleotide regulatory protein which has been suggested to mediate certain of insulin's actions on target tissues.
D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002772:Cholera Toxin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D037342:Pertussis Toxin; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D002772:Cholera Toxin; D011433:Propranolol; D037342:Pertussis Toxin; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000527:Alprostadil; D007545:Isoproterenol