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

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 (F-6 group). METHODS: 1 (insulin, 1 U . kg(-1)) was injected ip and 30 min later saline (F-6 + 1 group), H, G and E individually or combined (G + H, G + E, H + E and G + H + E) were all injected ip 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 ip 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 + Sat (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 (F-6 or F-6 + 1 groups). CONCLUSION: (a) Acute hyperglycemia is obtained from a condition of IIH by combined ip 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.