Effect of combined administration of counterregulatory hormones during insulin-induced hypoglycemia in rats: lipolysis mediated by a beta-adrenergic mechanism contributes to hyperglycemia.

The synergistic effect of combined injection of glucagon (G), cortisol (C) and phenylephrine+isoproterenol (E) during hypoglycemia in male adult Wistar rats was investigated. For this purpose we injected insulin (1 mg/kg) and 30 min later saline (controls), C (20 mg/kg), G (0.02 mg/kg), or E (1 mg/kg), individually or combined (G+C, G+E, C+E and C+G+E). All drugs were injected i.p. and all rats were killed 60 min after insulin injection. The rise in glycemia with C+G+E was greater (delta = 107 mg/dl) than the sum of the responses to injection of C, G and E individually, or in double combination plus any single hormone injection. This synergistic effect was reproduced by G + C + isoproterenol (Iso) but not by G + C + phenylephrine (delta = 0 mg/dl). The results also showed a clear relationship between hyperglycemia and lipolysis. Thus, lipolysis mediated by a beta-adrenergic mechanism played a significant role in promoting hyperglycemia when Iso was combined with G and C.