D'Alessio D A, Kieffer T J, Taborsky G J, Havel P J
Department of Medicine, University of Washington, Seattle, Washington 98195, USA. david.d'
J Clin Endocrinol Metab. 2001 Mar;86(3):1253-9. doi: 10.1210/jcem.86.3.7367.
Meal-induced insulin secretion is thought to be regulated primarily by absorbed nutrients and incretin hormones released from the gastrointestinal tract. In addition, the parasympathetic nervous system (PNS) is known to mediate preabsorptive, or cephalic phase, insulin secretion. Despite evidence that the PNS remains activated during the absorptive phase of the meal, its role in mediating postprandial insulin secretion has not been established. To study the role of the PNS in absorptive phase insulin release, we measured plasma concentrations of glucose as well as islet hormones and incretins in six healthy rhesus monkeys before and for 60 min after meals while they were infused with saline (control), atropine (muscarinic blockade), or trimethaphan (nicotinic blockade). During the infusion of saline, plasma levels of glucose, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1 increased promptly after meal ingestion and remained elevated throughout the 60 min of the study. The PP response was nearly abolished in animals treated with trimethaphan, indicating functional blockade of PNS input to the islet, and in contrast to the control study, there were minimal changes in plasma concentrations of glucose, incretin hormones, and insulin. Because trimethaphan inhibited glycemic and incretin stimuli in addition to blocking PNS input to the islet, it was not possible to discern the relative roles of these factors in the stimulation of insulin secretion. Atropine also significantly decreased PNS transmission to the islet, as reflected by PP levels similar to those observed with trimethaphan. Unlike the trimethaphan study, plasma glucose levels rose normally during atropine treatment and were similar to those in the control study over the course of the experiments (114 +/- 22 and 132 +/- 23 mmol/L.60 min, respectively). In addition, the rise in plasma glucagon-like peptide-1 following the meal was not suppressed by atropine, and the glucose-dependent insulinotropic polypeptide responses were only modestly decreased. Despite the significant increases in circulating glucose and incretins, plasma insulin levels were greatly attenuated by atropine, so that the 60 min responses were more comparable to those during trimethaphan treatment than to those in the control study (atropine, 3,576 +/- 1,284; trimethaphan, 4,128 +/- 2,616; control, 15,834 +/- 5,586 pmol/L.60 min; P: < 0.05). Thus, muscarinic blockade markedly suppressed the meal-induced insulin response despite normal postprandial glycemia and significant elevations of incretins. These results indicate that activation of the PNS during the absorptive phase of meals contributes significantly to the postprandial insulin secretory response.
餐食诱导的胰岛素分泌被认为主要受吸收的营养物质和胃肠道释放的肠促胰岛素激素调节。此外，已知副交感神经系统（PNS）介导吸收前或头期胰岛素分泌。尽管有证据表明在餐食吸收期PNS仍处于激活状态，但其在介导餐后胰岛素分泌中的作用尚未明确。为了研究PNS在吸收期胰岛素释放中的作用，我们在六只健康恒河猴进食前及进食后60分钟内，分别静脉输注生理盐水（对照）、阿托品（毒蕈碱阻断剂）或三甲噻方（烟碱阻断剂），同时测量血浆葡萄糖、胰岛激素和肠促胰岛素的浓度。在输注生理盐水期间，进食后血浆葡萄糖、胰多肽（PP）、胰岛素、葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1水平迅速升高，并在整个60分钟研究期间保持升高。在用三甲噻方治疗的动物中，PP反应几乎完全消失，这表明PNS向胰岛的输入功能被阻断，与对照研究相比，血浆葡萄糖、肠促胰岛素激素和胰岛素浓度变化极小。由于三甲噻方除了阻断PNS向胰岛的输入外，还抑制了血糖和肠促胰岛素刺激，因此无法区分这些因素在刺激胰岛素分泌中的相对作用。阿托品也显著降低了PNS向胰岛的传递，这通过与三甲噻方观察到的类似PP水平反映出来。与三甲噻方研究不同，在阿托品治疗期间血浆葡萄糖水平正常升高，并且在实验过程中与对照研究相似（分别为114±22和132±23 mmol/L.60分钟）。此外，餐后血浆胰高血糖素样肽-1的升高未被阿托品抑制，葡萄糖依赖性促胰岛素多肽反应仅略有降低。尽管循环葡萄糖和肠促胰岛素显著增加，但阿托品使血浆胰岛素水平大幅降低，因此60分钟反应与三甲噻方治疗期间的反应比对照研究中的反应更具可比性（阿托品，3576±1284；三甲噻方，4128±2616；对照，15834±5586 pmol/L.60分钟；P：<0.05）。因此，尽管餐后血糖正常且肠促胰岛素显著升高，毒蕈碱阻断仍显著抑制了餐食诱导的胰岛素反应。这些结果表明，餐食吸收期PNS的激活对餐后胰岛素分泌反应有显著贡献。
