AUTONOMIC CONTROL OF PANCREATIC-POLYPEPTIDE AND GLUCAGON-SECRETION DURING NEUROGLUCOPENIA AND HYPOGLYCEMIA IN MICE

Neural control of pancreatic polypeptide (PP) release has not been pre viously investigated in the mouse. In addition, it is not known to wha t extent increased glucagon secretion during hypoglycemia in mice is n eurally mediated vs. an effect of hypoglycemia to directly stimulate g lucagon secretion at the level of the islet. Feeding or the cholinergi c agonist carbachol increased plasma PP levels in conscious mice (+74 +/- 18 pg/ml vs. fasted mice and +141 +/- 17 pg/ml vs. control, respec tively). Neuroglucopenia induced by 2-deoxy-D-glucose or insulin-induc ed hypoglycemia also increased plasma PP (+79 +/- 18 and +89 +/- 11 pg /ml vs. control, respectively). These increases were abolished by hexa methonium and reduced by atropine methylnitrate (atropine). Hypoglycem ia-induced hyperglucagonemia (+1,243 +/- 275 pg/ml) was reduced to 31 +/- 7% of control by atropine (+382 +/- 85 pg/ml), to 48 +/- 9% of con trol by combined adrenergic blockade (+601 +/- 112 pg/ml), and nearly abolished by atropine plus combined blockade (+143 +/- 41 pg/ml; 11 +/ - 3% of control) or hexamethonium (+151 +/- 38 pg/ml; 12 +/- 3% of con trol). We conclude the following in the mouse. 1) Feeding or cholinerg ic agonists increase plasma PP. 2) During neuroglucopenia or hypoglyce mia, plasma PP is increased via nicotinic and muscarinic mechanisms. 3 ) The glucagon response to hypoglycemia is predominantly the result of autonomic activation and is mediated by both muscarinic and adrenergi c mechanisms.