OBJECTIVES Gastrointestinal hormones contribute to the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB) on glycemic control. Secretin is secreted from duodenal S cells in response to low luminal pH, but it is unknown whether its secretion is altered after RYGB and if secretin contributes to the postoperative improvement in glycemic control. We hypothesized that secretin secretion increases after RYGB as a result of the diversion of nutrients to more distal parts of the small intestine, and thereby affects islet hormone release. METHODS A specific secretin radioimmunoassay was developed, evaluated biochemically, and used to quantify plasma concentrations of secretin in 13 obese individuals before, 1 week after, and 3 months after RYGB. Distribution of secretin and its receptor was assessed by RNA sequencing, mass-spectrometry and in situ hybridization in human and rat tissues. Isolated, perfused rat intestine and pancreas were used to explore the molecular mechanism underlying glucose-induced secretin secretion and to study direct effects of secretin on glucagon, insulin, and somatostatin secretion. Secretin was administered alone or in combination with GLP-1 to non-sedated rats to evaluate effects on glucose regulation. RESULTS Plasma postprandial secretin was more than doubled in humans after RYGB (P < 0.001). The distal small intestine harbored secretin expressing cells in both rats and humans. Glucose increased the secretion of secretin in a sodium-glucose cotransporter dependent manner when administered to the distal part but not into the proximal part of the rat small intestine. Secretin stimulated somatostatin secretion (fold change: 1.59, P < 0.05) from the perfused rat pancreas but affected neither insulin (P = 0.2) nor glucagon (P = 0.97) secretion. When administered to rats in vivo, insulin secretion was attenuated and glucagon secretion increased (P = 0.04), while blood glucose peak time was delayed (from 15 to 45 min) and gastric emptying time prolonged (P = 0.004). CONCLUSIONS Glucose-sensing secretin cells located in the distal part of the small intestine may contribute to increased plasma concentrations observed after RYGB. The metabolic role of the distal S cells warrants further studies.

中文翻译：

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Roux-en-Y 胃旁路手术后的分泌素释放揭示了远端小肠中的葡萄糖敏感 S 细胞群。

目的 胃肠激素有助于 Roux-en-Y 胃绕道手术 (RYGB) 对血糖控制的有益影响。十二指肠 S 细胞在响应低管腔 pH 值时分泌促胰液素，但在 RYGB 后其分泌是否发生改变以及促胰液素是否有助于术后血糖控制的改善尚不清楚。我们假设 RYGB 后促胰液素分泌增加，这是由于营养物质转移到小肠的更远端部分，从而影响胰岛激素的释放。方法 开发了一种特异性促胰液素放射免疫测定法，对其进行生化评估，并用于量化 13 名肥胖个体在 RYGB 之前、之后 1 周和之后 3 个月的血浆促胰液素浓度。通过 RNA 测序评估促胰液素及其受体的分布，人类和大鼠组织中的质谱和原位杂交。分离的、灌注的大鼠肠道和胰腺用于探索葡萄糖诱导促胰液素分泌的分子机制，并研究促胰液素对胰高血糖素、胰岛素和生长抑素分泌的直接影响。将分泌素单独或与 GLP-1 联合给予非镇静大鼠以评估对葡萄糖调节的影响。结果 RYGB 后人类血浆餐后促胰液素增加了一倍以上（P < 0.001）。在大鼠和人类中，远端小肠都含有表达分泌素的细胞。葡萄糖在大鼠小肠远端而不是近端给药时以钠-葡萄糖协同转运蛋白依赖性方式增加促胰液素的分泌。分泌素刺激生长抑素分泌（倍数变化：1.59，P < 0.05) 来自灌注的大鼠胰腺，但既不影响胰岛素 (P = 0.2) 也不影响胰高血糖素 (P = 0.97) 的分泌。大鼠体内给药时，胰岛素分泌减弱，胰高血糖素分泌增加（P = 0.04），而血糖峰值时间延迟（15至45分钟），胃排空时间延长（P = 0.004）。结论 位于小肠远端的葡萄糖敏感促胰液素细胞可能有助于 RYGB 后观察到的血浆浓度增加。远端 S 细胞的代谢作用值得进一步研究。而血糖峰值时间延迟（从15到45分钟），胃排空时间延长（P = 0.004）。结论 位于小肠远端的葡萄糖敏感促胰液素细胞可能有助于 RYGB 后观察到的血浆浓度增加。远端 S 细胞的代谢作用值得进一步研究。而血糖峰值时间延迟（从15到45分钟），胃排空时间延长（P = 0.004）。结论 位于小肠远端的葡萄糖敏感促胰液素细胞可能有助于 RYGB 后观察到的血浆浓度增加。远端 S 细胞的代谢作用值得进一步研究。