AJP - Endocrinology and Metabolism, Vol 248, Issue 3 299-E303, Copyright © 1985 by American Physiological Society
Carbachol modulates GIP-mediated insulin release from rat pancreatic lobules in vitro
A. J. McCullough, J. B. Marshall, C. P. Bingham, B. L. Rice, L. D. Manning and S. C. Kalhan
Rat pancreatic lobules were used to investigate the interaction of gastric
inhibitory polypeptide (GIP), carbachol, glucose, and an amino acid mixture
on insulin secretion. At 5 mM glucose, GIP (1.1 ng/ml) did not augment
insulin secretion in the presence or absence of carbachol (5 X 10(-5)M)
during a 210-min incubation. However, at 11 mM glucose, GIP did augment
insulin secretion in the presence (342.5 +/- 62.0 vs. 212.5 +/- 50.5 microU
. ml-1 . mg tissue-1, mean +/- SE; P less than 0.01) but not the absence
(217.0 +/- 45.5 vs. 205.8 +/- 35.0 microU . ml-1 . mg tissue-1) of
carbachol. During subsequent 30-min incubations, GIP was increased to a
supra-physiological concentration of 11 ng/ml and again augmented insulin
secretion with (65.8 +/- 10.8 vs. 27.8 +/- 2.4 microU . ml-1 . mg tissue-1
. h-1; P less than 0.001) but not without (37.2 +/- 1.8 vs. 30.2 +/- 2
microU . ml-1 . mg-1 tissue-1 . h-1) carbachol present. This GIP-mediated
insulin secretion was blocked by atropine (34.8 to 1.8 vs. 37.6 +/- 1.6
microU . ml-1 . mg tissue-1 . h-1). At amino acid concentrations of 21 and
211 mM, but not 2.1 mM, GIP augmented insulin release but again only with
carbachol present. In conclusion, porcine GIP augments amino acid as well
as glucose-mediated insulin secretion in vitro. Furthermore, this
biological action is dependent on an, as yet, unidentified cholinergic
mechanism. The pathophysiological significance of the neural-hormonal
interaction deserves further investigation.
