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) secretion during hypoglycemia in the rat, insulin was administered to chronically cannulated rats, and plasma PP responses were compared between saline-treated animals and animals pretreated with a ganglionic blocking agent (hexamethonium), a muscarinic antagonist (atropine), combined α- and β-adrenergic receptor blockade (propranolol + tolazoline), or combined adrenergic blockade + atropine. PP was measured using a new RIA which selectively detects PP in rat plasma. In control rats (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) (ΔPP = +241 ± 42 pg/ml, P < 0.0005), demonstrating that in rats, as in other species, insulin-induced hypoglycemic 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. control animals). Thus, at least 90% of the PP response to hypoglycemic is neurally mediated. The plasma PP response to hypoglycemic was +85 ± 24 pg/ml in atropine-treated rats (P 0.01 vs. control rats), suggesting that approximately 65% of the PP response is mediated via muscarinic acetylcholine receptors on the islet F cell. The PP response to hypoglycemia in rats with combined adrenergic blockade (Δ = +168 ± 32 pg/ml) was slightly, but not significantly smaller than that in control rats. The combination of combined blockade + atropine resulted in a PP response (Δ = +26 ± 7 pg/ml) to hypoglycemia that was similar to that in hexamethonium-treated rats (P < 0.01 vs. control rats). These results suggest: 1) The PP response to hypoglycemia is predominetely the result of muscarinic, cholinergic activation. 2) There is a minor adrenergic contribution to the response. 3) The plasma PP response mey be useful as an index of autonomic neural input to the islet during hypoglycemia.