Effect of glucagon on carbohydrate metabolism in Zucker fatty rats

In response to arginine infusion, Zucker fatty rats developed hyperglycemia accompanying hyperglucagonemia and hyperinsulinemia. The hyperglycemia could not be explained by changes in the ratio of glucagon/insulin. However, arginine infusion failed to increase plasma glucose in fatty rats pretreated with anti-glucagon serum, suggesting a hyperglycemic effect of glucagon released by arginine. Kinetic studies of glucose metabolism revealed that the rates of glucose appearance (Ra) and glucose disappearance (Rd) of lean rats rapidly and simultaneously increased to the same extent after the start of arginine infusion. By contrast, in fatty rats, Ra markedly increased immediately after the start of the infusion, but Rd did not significantly increase until hyperglycemia was established. Overall insulin sensitivity of fatty rats was markedly reduced, determined by the steady state plasma glucose method. We conclude tht arginine-induced hyperglycemia in fatty rats is caused by enhanced glucose output from the liver due to hyperglucagonemia and/or by decreased glucose utilization due to insulin resistance.