ROLE OF EPINEPHRINE DURING INSULIN-INDUCED HYPOGLYCEMIA IN FASTED RATS

Responses to insulin-induced hypoglycemia in fasted sham-operated (SHA M), adrenodemedullated (ADM), and epinephrine-infused ADM (ADM + E) ra ts were studied to ascertain the specific role of epinephrine in incre asing resting skeletal muscle content of adenosine 3',5'-cyclic monoph osphate (cAMP) and fructose 2,6-bisphosphate (F-2,6-P-2,), which are i nvolved in stimulation of muscle glycogenolysis and lactate production . Rats from each group were fasted for 24 h and then infused intraveno usly with insulin (30, 60, or 90 min) to produce plasma insulin values of similar to 92 mu U/ml. One-half of the insulin-infused ADM rats we re also infused with epinephrine (ADM + E). Muscle and blood lactate, muscle cAMP, and muscle F-2,6-P, increased and muscle glycogen decreas ed in SHAM rats. Each of these changes was prevented or attenuated in ADM rats and restored in ADM + E rats. Liver cAMP, glycogen, and F-2,6 -P, responses to hypoglycemia were similar in SHAM, ADM, and ADM + E r ats. Blood glucose decreased to 0.74 +/- 0.05 mM in ADM rats compared with 1.54 +/- 0.11 mM in SHAM and 1.34 +/- 0.15 mM in ADM + E rats aft er 90 min of insulin infusion. The increase in plasma epinephrine is t herefore essential in the counterregulatory response to insulin-induce d hypoglycemia in fasted rats. Resting skeletal muscle glycogenolysis and lactate production for hepatic gluconeogenic substrate appear to b e important components of the counterregulatory response in fasted rat s.