Adrenergic control of the glucagon response to ammonia in the perfused rat pancreas

The isolated perfused rat pancreas was used to investigate how adrenergic influences within the pancreas might mediate ammonia-induced glucagon secretion. The addition of 2 mM ammonia to the perfusate increased norepinephrine release and glucagon secretion in the effluent. Upon cessation of ammonia addition, a pronounced burst of glucagon release was observed. Alpha-adrenergic blockade with phentolamine (10 microM) blocked the glucagon response to ammonia. Beta-adrenergic blockade with propranolol (10 microM) had no significant effect on the amount of glucagon release induced by ammonia. Depletion of norepinephrine from sympathetic nerve terminals by pretreatment with 6-hydroxydopamine lowered the pancreatic norepinephrine content to less than 16% of the control value and diminished the glucagon and norepinephrine response to ammonia almost completely. The burst of glucagon release after the removal of ammonia was inhibited to 2% of the control value by phentolamine and to 57% by propranolol. Pretreatment with 6-hydroxydopamine reduced the burst of glucagon secretion to 28% of the control value. Neither phentolamine nor propranolol reduced the magnitude of the ammonia-induced suppression of insulin secretion. We conclude that the effect of ammonia on glucagon release from the isolated rat pancreas is mediated by intrapancreatic adrenergic control.