Gastrointestinal augmentation of insulin secretion observed in response to glucose ingestion may be largely mediated by gastric inhibitory polypeptide (GIP). Since the enteric signal potentiating insulin secretion is blunted by atropine, we studied the effects of this drug on glucose-stimulated GIP secretion in normal subjects. Eight individuals, studied on two occasions, were given intraduodenal glucose (75 gm. over 60 minutes) by perfusion tube, on one occasion with intravenous atropine (15 μg. per kilogram bolus followed by 17 μg. per minute for 60 minutes) and on another occasion with intravenous saline (control). Comparing the results of atropine and control studies, mean serum immunoreactive GIP (IRGIP) was significantly lower at 5 and 15 minutes (444 ± 82 vs. 277 ± 44, p < 0.05 and 1,072 ± 151 vs. 427 ± 74 pg./ml., p < 0.02 at 5 and 15 minutes, respectively), and the integrated incremental area under the 120-minute curve was significantly less (62,170 ± 11,880 vs. 91,820 ± 14,200 pg. ·minute·ml.−1 p < 0.05) with atropine. Serum IRI levels were also significantly lower during the atropine studies (28 ± 8 vs. 14 ± 2, p < 0.05, 54 ± 7 vs. 25 ± 5, p < 0.02, 62 ± 8 vs. 36 ± 7 μU. per milliliter, p < 0.05, at 15, 30, and 45 minutes, respectively). The integrated incremental area under the IRGIP curve was reduced about 33 per cent, while the area under the IRI curve was reduced about 45 per cent by atropine. In a second group of similar experiments substituting d-xylose for glucose, the effect of atropine on d-xylose absorption was studied in normal subjects. Atropine did not alter d-xylose absorption during the first hour, but significantly enhanced its absorption during the second hour, as compared with control studies. We conclude that atropine blunts the rise in serum IRGIP normally stimulated by intestinal glucose perfusion, which is probably a direct effect of the drug on the gastrointestinal tract, as opposed to an effect mediated by inhibition of glucose absorption. These observations are consistent with the hypothesis that GIP is the enteric signal potentiating insulin secretion that is attenuated by atropine.

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