In man, a vagotomy and pyloroplasty results in an augmented gastric inhibitory polypeptide (GIP) response to glucose. To further delineate the role of the parasympathetic autonomic nervous system on GIP homeostasis, this study evaluated the effect of parasympathomimetic and parasympatholytic drugs on fasting and glucose-stimulated GIP. Six awake dogs with Mann-Bollman fistulas underwent three studies where 50 ml of 20% d-glucose was infused intraduodenally (ID) over 10 min. In two of these studies either atropine (20 μg/kg/hr) or bethanechol (150 μg/kg/hr) was infused intravenously (IV) for 30 min before and 120 min after ID glucose. In a fourth study, 50 ml of 0.1% acetylcholine (Ach) was infused ID for 10 min. Venous samples (every 15 min) were assayed for IR-GIP. ID Ach caused (P < 0.05) reductions in fasting IR-GIP at 45, 60, 90, and 120 min. IV atropine and IV bethanechol had no effect on fasting IR-GIP. Following ID glucose, IR-GIP increased at 15 and 30 min in all three studies. Compared to ID glucose, the IR-GIP response to IV bethanechol + ID glucose was significantly less at 15, 30, and 45 min. In addition, the integrated, incremental IR-GIP area was significantly less. The IR-GIP response to IV atropine + ID glucose was no different than the IR-GIP response to ID glucose alone. This study demonstrates that parasympathomimetic drugs decrease fasting GIP and blunt the GIP response to ID glucose, suggesting a physiologic role for the parasympathetic neuroendocrine system in modulating the GIP response to glucose.
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