INDEPENDENCE OF GIP-INDUCED INSULIN-SECRETION FROM SYMPATHETIC AND PARASYMPATHETIC INNERVATION IN THE ISOLATED PERFUSED RAT PANCREAS

The incretin candidate GIP (gastric inhibitory polypeptide) is released from the gut by nutrients and can stimulate insulin secretion. Metabolic and hormonal factors have been shown to modulate insulin response to GIP. It is unknown, however, whether the autonomic nervous system, which itself controls insulin secretion, can modulate the insulinotropic effect of GIP. In the isolated perfused rat pancreas, we therefore investigated the influence of sympathetic and parasympathetic agonists and antagonists on the insulin response to GIP. As compared to control (6990 +/- 890-mu-U/1O min), the effect of either acetylcholine (29030 +/- 4600-mu-U/10 min), atropine (5880 +/- 1740-mu-U/10 min), norepinephrine (2520 +/- 750-mu-U/10 min), phentolamine(11380 +/-1910-mu-U/10 min), isoproterenol (12740 +/- 2090-mu-U/10 min), propranolol (5600 +/- 880-mu-U/10 min), or GIP (29660 +/- 4490-mu-U/10 min) on insulin secretion was consistent with previous reports. The effects of the combined administration of GIP and either acetylcholine (48140 +/- 7540-mu-U/10 min), phentolamine (43930 +/- 4490-mu-U/10 min), norepinephrine (9000 +/- 1740-mu-U/10 (min), or isoproterenol (36280 +/- 5210-mu-U/10 min) on insulin release were additive. Insulin response to GIP was resistant to atropine (24210 +/-9470-mu-U/10 min) and propranolol (26450 +/- 4930-mu/10 min). We conclude that both GIP and the autonomic nervous system influence insulin secretion, but that they do so independently from each other.