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.
Souza
H M
HM
Departamento de Ciências Fisiológicas, Universidade Estadual de Londrina, PR, Brasil.
Hell
N S
NS
Lopes
G
G
Bazotte
R B
RB
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005765:Gastrointestinal Agents / Q000008:administration & dosage; D005934:Glucagon / Q000008:administration & dosage; D006854:Hydrocortisone / Q000008:administration & dosage; D007003:Hypoglycemia / Q000139:chemically induced / Q000188:drug therapy*; D007328:Insulin; D007545:Isoproterenol / Q000008:administration & dosage; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D010656:Phenylephrine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D005765:Gastrointestinal Agents; D007328:Insulin; D010656:Phenylephrine; D005934:Glucagon; D007545:Isoproterenol; D006854:Hydrocortisone