IMPROVEMENT IN BLUNTED GLUCAGON-RESPONSE TO INSULIN-INDUCED HYPOGLYCEMIA BY STRICT GLYCEMIC CONTROL IN DIABETICS

To elucidate the mechanism of impaired pancreatic A cell function in h ypoglycemia in diabetics, the effect of long-term strict glycemic regu lations on hypoglycemia-induced glucagon secretion was studied. Firstl y, the effect of plasma insulin concentrations on suppressing A cell w as studied in healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. With 0.3 U/kg of insulin, the rate of fall in glyce mia and the nadir of blood glucose were made similar to those with 0.1 U/kg of insulin by glucose infusion with artificial endocrine pancrea s. Plasma glucagon response after 0.3 U/kg of insulin was significantl y suppressed as compared to that after 0.1 U/kg of insulin, demonstrat ing that not only hypoglycemic stimulus but also plasma insulin concen tration were important determinants responsible for glucagon secretion in insulin-induced hypoglycemia. Secondly, effect of strict glycemic control was studied. Short-acting insulin at a dose of 0.1 U/kg was in jected in an intravenous bolus form into 12 insulin-dependent (IDDM) a nd 9 non-insulin-dependent (NIDDM) diabetics before and 1-3 months aft er strict glycemic control with multiple insulin injections therapy. B efore strict glycemic regulations in IDDM, no significant rise in plas ma glucagon concentrations was observed during the insulin-induced hyp oglycemia. In NIDDM, a rise in plasma glucagon concentrations was obse rved, though the response was delayed. After strict glycemic regulatio ns, in patients with residual endogenous insulin secretion, the glucag on response to hypoglycemia improved considerably in IDDM and normaliz ed in NIDDM. In IDDM and NIDDM, improvement in glucagon response to hy poglycemia related positively to daily urinary secretion rate of C-pep tide. From these experiments, it is clearly shown that blunted hypogly cemia induced glucagon secretion in diabetics is secondary to poor gly cemic control, and that the existence of endogenous insulin secretion is essential to glucagon response to hypoglycemia.