Effects of antecedent hypoglycemia, antecedent hyperinsulinemia, and antecedent corticosterone on subsequent counterregulation in normal rats

This study examined the effects of antecedent hypoglycemia, antecedent hyperinsulinemia, and antecedent increases in plasma corticosterone on subsequent counterregulatory responses to hypoglycemia in normal rats. Four days of intermittent treatment with antecedent hypoglycemia and antecedent hyperinsulinemia resulted in impaired epinephrine responses to subsequent hypoglycemia on the fifth day. This correlated with the diminished incremental increase of hepatic glucose production during the hypoglycemic clamp in these groups. Surprisingly, rats that had undergone antecedent corticosterone also displayed impaired glucose production response in spite of normal neuroendocrine counterregulation. We conclude that both antecedent hypoglycemia and antecedent hyperinsulinemia may cause defective hormonal counterregulation leading to impaired glucose production during subsequent hypoglycemia. This suggests that antecedent hyperinsulinemia per se plays an important role in the pathogenesis of hypoglycemia-associated autonomic failure. Moreover, antecedent increases in corticosterone may cause deficient glucose production without altering the neuroendocrine responses to hypoglycemia, implying that other mechanisms might be involved.