Pj. Havel et al., AUTONOMIC NERVOUS-SYSTEM MEDIATION OF THE PANCREATIC-POLYPEPTIDE RESPONSE TO INSULIN-INDUCED HYPOGLYCEMIA IN CONSCIOUS RATS, Endocrinology, 130(4), 1992, pp. 2225-2229
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.