COUNTERREGULATION BY EPINEPHRINE AND GLUCAGON DURING INSULIN-INDUCED HYPOGLYCEMIA IN THE CONSCIOUS DOG

We assessed the combined role of epinephrine and glucagon in regulatin g gluconeogenic precursor metabolism during insulin-induced hypoglycem ia in the overnight-fasted, adrenalectomized, conscious dog. In paired studies (n = 5) insulin was infused intraportally al 5 mU . kg(-1) . min(-1) for 3 h. Epinephrine was infused at a basal rate (B-EPI) or va riable rate to simulate the normal epinephrine response to hypoglycemi a (H-EPI), whereas in both groups the hypoglycemia-induced rise in cor tisol was simulated by cortisol infusion. Plasma glucose fell to simil ar to 42 mg/dl in both groups. Glucagon failed to rise in B-EPI, but i ncreased normally in H-EPI. Hepatic glucose release fell in B-EPI but increased in H-EPI. In B-EPI, the normal rise in lactate levels and ne t hepatic lactate uptake was prevented. Alanine and glycerol metabolis m were similar in both groups. Since glucagon plays little role in reg ulating gluconeogenic precursor metabolism during 3 h of insulin-induc ed hypoglycemia, epinephrine must be responsible for increasing lactat e release from muscle, but is minimally involved in the lipolytic resp onse. In conclusion, a normal rise in epinephrine appears to be requir ed to elicit an increase in glucagon during insulin-induced hypoglycem ia in the dog. During insulin-induced hypoglycemia, epinephrine plays a major role in maintaining an elevated rate of glucose production, pr obably via muscle lactate release and hepatic lactate uptake.