Synergistic effect of counterregulatory hormones during insulin-induced hypoglycemia in rats: participation of lipolysis and gluconeogenesis to hyperglycemia.

AIM

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).

CONCLUSION

(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.