Effect of 2-bromostearate on glucose-phosphorylating activities and the dynamics of insulin secretion in islets of Langerhans during fasting.
Glucose-phosphorylating activity and insulin secretion were measured in homogenates of isolated rat islets and of perfused rat pancreas, respectively. Fasting for 96 h produced a significant decrease of both low-and high-Km glucose-phosphorylating activities and blocked the insulin secretory response to glucose. In the presence of glucose, 0.25 mM 2-bromostearate, a known inhibitor of fatty acid oxidation, partially restored the insulin response to glucose that was lost during fasting. This effect paralleled the restoration of glucose-phosphorylation activities (primarily the high-Km component) seen when islets isolated from 96-h-fasted rats were preincubated with 0.25 mM 2-bromostearate. It is concluded that fasting-induced adaptations of glucose-phosphorylating enzymes could account, at least in part, for the reduced insulin secretory response to glucose. 2-Bromostearate, an inhibitor of fatty acid oxidation, is able to restore both insulin secretory response and glucose-phosphorylating activities, suggesting possible interrelations among the correlated impairment in insulin secretion, islet glucose-phosphorylating activity, islet glucose metabolism, and the oxidation of fatty acids in the B-cell during fasting.
D000818:Animals; D005215:Fasting; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013229:Stearic Acids / Q000494:pharmacology*
D007328:Insulin; D013229:Stearic Acids; C000320:2-bromostearic acid; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose