METABOLIC EFFECTS OF HYPOGLYCEMIC COUNTERREGULATION DURING SUSTAINED MILD HYPERINSULINEMIA AND CONSTANT GLUCOSE AVAILABILITY IN HEALTHY-MEN

Posthypoglycemic metabolic changes have been studied predominantly dur ing waning of insulin action. We evaluated the effects of hypoglycemic counterregulation on glucose and lipid metabolism during continuous i nsulin infusion. Glucose was infused at a constant rate throughout the study (4 mg.kg(-1).min(-1)). During the second part of the study, pla sma glucose levels were clamped at similar to 4 mM by variable insulin infusion. In six subjects, but not in five control subjects, short-te rm hypoglycemia (nadir plasma glucose 2.80 +/- 0.05 mM) was induced by an additional bolus injection of insulin before starting insulin infu sion. Substrate oxidation rates and plasma substrate fluxes were deter mined by indirect calorimetry and primed continuous infusions of [3-H- 3]glucose and [C-14]palmitate. After hypoglycemia, higher insulin infu sion rates than in the control group were required to clamp plasma glu cose concentrations at similar levels (p < 0.05). Additionally, insuli n levels were increased compared with those in control subjects (p < 0 .01). There were no differences in substrate oxidation rates, hepatic glucose production, or lipolysis after hypoglycemia. In conclusion, th e counterregulatory hormonal response after short-lasting mild hypogly cemia with sustained modest hyperinsulinemia and constant glucose avai lability induces insulin resistance with respect to glucose uptake but is unable to stimulate hepatic glucose production or lipolysis.