RESPONSE TO INTRAVENOUS INJECTIONS OF AMYLIN AND GLUCAGON IN FASTED, FED, AND HYPOGLYCEMIC RATS

The actions of intravenous glucagon and amylin, a newly discovered hyperglycemic pancreatic islet hormone, have been compared in 20-h fasted and fed, tightly anesthetized rats, and in rats made hypoglycemic with an insulin infusion. In fasted animals, amylin (75 nmol/kg) was more effective than glucagon (90 nmol/kg) in increasing plasma glucose (glucose increment 4.55 vs. 1.71 mM, P < 0.001). Amylin elicited a marked increase in plasma lactate, as previously reported, whereas glucagon did not alter plasma lactate. In fed animals, glucagon elicited twice as much increase in plasma glucose as did amylin; amylin again elicited a marked lactate increase that was greater (increment 1.45 vs. 0.97 mM, P < 0.05) and more prolonged than in the fasted state, whereas glucagon was without effect on lactate levels. These findings are consistent with glucagon's known action to promote hyperglycemia from hepatic glycogenolysis and amylin's demonstrated action to promote muscle glycogenolysis and increase lactate supply to the liver. Infusions of sodium lactate that produced plasma lactate increments similar to those evoked by 75 nmol/kg amylin evoked patterns of glucose response in fasted and fed rats similar to those evoked by amylin. Thus increased lactate supply to the liver may account for amylin's hyperglycemic effects. Amylin and glucagon could each restore plasma glucose to control levels in fasted animals made hypoglycemic by insulin infusion (plasma glucose reduced to 3.3 mM). A bolus of 75 nmol/kg amylin was more effective than 180 nmol/kg glucagon, restoring basal glucose levels for >3 h, whereas glucagon restored it for <1 h. Combining boluses of glucagon and amylin produced responses that were at least additive, perhaps reflecting the simultaneous supply of gluconeogenic substrate by amylin action on muscle and stimulation of hepatic gluconeogenic pathways by glucagon.