AUTONOMIC NERVOUS-SYSTEM MEDIATION OF THE PANCREATIC-POLYPEPTIDE RESPONSE TO INSULIN-INDUCED HYPOGLYCEMIA IN CONSCIOUS RATS

To investigate the neural regulation of pancreatic polypeptide (PP) se cretion during hypoglycemia in the rat, insulin was administered to ch ronically cannulated rats, and plasma PP responses were compared betwe en saline-treated animals and animals pretreated with a ganglionic blo cking agent (hexamethonium), a muscarinic antagonist (atropine), combi ned alpha- and beta-adrenergic receptor blockade (propranolol + tolazo line), or combined adrenergic blockade + atropine. PP was measured usi ng a new RIA which selectively detects PP in rat plasma. In control ra ts (n = 10), plasma PP increased from a baseline level of 30 +/- 3 pg/ ml to 271 +/- 41 pg/ml during hypoglycemia (plasma glucose = 29 +/- 2 mg/dl) (DELTA-PP = +241 +/- 42 pg/ml, P < 0.0005), demonstrating that in rats, as in other species, insulin-induced hypoglycemia is a potent stimulus for PP release. PP only increased by 31 +/- 10 pg/ml during similar hypoglycemia in 7 hexamethonium-treated rats (P < 0.01 vs. con trol animals). Thus, at least 90% of the PP response to hypoglycemia i s neurally mediated. The plasma PP response to hypoglycemia was +85 +/ - 24 pg/ml in atropine-treated rats (P 0.01 vs. control rats), suggest ing that approximately 65% of the PP response is mediated via muscarin ic acetylcholine receptors on the islet F cell. The PP response to hyp oglycemia in rats with combined adrenergic blockade (DELTA = +168 +/- 32 pg/ml) was slightly, but not significantly smaller than that in con trol rats. The combination of combined blockade + atropine resulted in a PP response (DELTA = +26 +/- 7 pg/ml) to hypoglycemia that was simi lar to that in hexamethonium-treated rats (P < 0.01 vs. control rats). These results suggest: 1) The PP response to hypoglycemia is predomin ately the result of muscarinic, cholinergic activation. 2) There is a minor adrenergic contribution to the response. 3) The plasma PP respon se may be useful as an index of autonomic neural input to the islet du ring hypoglycemia.