Synergistic effect of counterregulatory hormones during insulin-induced hypoglycemia in rats: participation of lipolysis and gluconeogenesis to hyperglycemia.
OBJECTIVE
To study the synergistic effect of G (glucagon, 0.02 mg.kg-1), H (hydrocortisone, 20 mg.kg-1) and E (phenylephrine + isoproterenol, both 1 mg.kg-1) during insulin-induced hypoglycemia (IIH) in rats with 6 h of food deprivation (F6 group).


METHODS
I (insulin, 1 U.kg-1) was injected i.p. and 30 min later saline (F6 + I group), H, G and E individually or combined (G + H, G + E, H + E and G + H + E) were all injected i.p. and all experiments started 1 h after I injection.


RESULTS
The rise in glycemia with H + G + E was greater than the sum of the responses to i.p. H, G and E individually or in double combination plus any single hormone. This effect was reproduced by G + H + Iso (isoproterenol, 1 mg.kg-1), G + H + Iso + Met (metoprolol, 1 mg.kg-1) and G + H + Sal (salbutamol, 1 mg.kg-1). A clear relationship was shown between glycemia and free fatty acids levels. Liver gluconeogenesis from glycerol (2 mmol.L-1) was higher in the group which received G + H + beta-adrenergic agonist vs control rats (F6 or F6 + I groups).


CONCLUSIONS
(a) Acute hyperglycemia is obtained from a condition of IIH by combined i.p. of G + H + beta-adrenergic agonists; (b) This effect cannot be ascribed to a single hormone, but is a consequence of the combined effects of these substances; (c) Blood insulin levels and liver glycogen have no participation; (d) Lipolysis mediated by a beta-adrenergic mechanism and gluconeogenesis from glycerol contribute to the hyperglycemia.
Souza
H M
HM
Departamento de Ciências Fisiológicas, Universidade Estadual de Londrina, PR, Brazil.
Hell
N S
NS
Lopes
G
G
Bazotte
R B
RB
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004357:Drug Synergism; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis; D006854:Hydrocortisone / Q000494:pharmacology; D006943:Hyperglycemia / Q000209:etiology*; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007328:Insulin; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008112:Liver Glycogen; D010656:Phenylephrine; D005934:Glucagon; D007545:Isoproterenol; D006854:Hydrocortisone