低细胞外 pH 会抑制肠道 L 细胞释放 GLP-1。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Obesity Pub Date : 2024-09-05 DOI:10.1002/oby.24125
Philippa Garbutt, Malgorzata Cyranka, Johanna Michl, Yuko Maejima, Natascia Vedovato, Kenju Shimomura, Pawel Swietach, Heidi de Wet
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引用次数: 0

摘要

目的:从胃到直肠,肠腔 pH 值各不相同,在疾病时会发生紊乱。然而,人们对增量素激素分泌的 pH 依赖性知之甚少,大多数体外研究都没有考虑这一调节因素,或者使用的是非生理缓冲系统。在此,我们报告了胰高血糖素样肽-1(GLP-1)从L细胞外排的细胞外pH值(pHe)依赖性:方法:通过 ELISA 检测 GLUTag 细胞和小鼠体外原代肠道培养物中 GLP-1 释放的 pHe 依赖性。在生理(CO2/HCO3-)缓冲体系和无生理(HEPES缓冲液)缓冲体系的情况下,在一定的pHe范围内测量了GLP-1的释放。鉴于pH敏感性中至少有一部分可能来自细胞内,因此绘制了细胞内pH(pHi)和pHe之间的关系图:结果:L 细胞的 GLP-1 分泌是 pHe 依赖性的,在碱性条件下会受到刺激。pHi随pHe的变化而变化,但在没有CO2/HCO3-缓冲液的情况下,这种关系会被偏移到更碱性的水平,如果用葡萄糖酸盐等渗补偿通常伴随[HCO3-]变化的[Cl-]变化,这种关系会变得更浅:结论:GLP-1 的分泌对 pHe 和存在的缓冲液很敏感。结论:GLP-1 的分泌对 pHe 和存在的缓冲液很敏感,利用这一机制进行治疗可能会使肥胖症患者受益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The release of GLP-1 from gut L cells is inhibited by low extracellular pH

Objective

The intestinal luminal pH profile varies from stomach to rectum and becomes disrupted in diseases. However, little is known about the pH dependence of incretin hormone secretion, with most in vitro studies having failed to consider this modulatory factor or having used nonphysiological buffer systems. Here, we report the extracellular pH (pHe) dependence of glucagon-like peptide-1 (GLP-1) exocytosis from L cells.

Methods

The pHe dependence of GLP-1 release from GLUTag cells and murine ex vivo primary gut cultures was detected by ELISA. GLP-1 release was measured over a range of pHe under a physiological (CO2/HCO3) buffering regime and in its absence (HEPES buffer). The relationship between intracellular pH (pHi) and pHe was mapped given that at least some component of pH sensitivity is likely to be intracellular.

Results

GLP-1 secretion from L cells was pHe-dependent and stimulated under alkaline conditions. In the absence of glucose or extracellular calcium, secretion remained at a pHe-insensitive baseline. pHi followed changes in pHe, but the relationship was offset to more alkaline levels in the absence of CO2/HCO3 buffer and became shallower if [Cl] changes that normally accompany [HCO3] changes were compensated iso-osmotically with gluconate.

Conclusions

GLP-1 secretion is sensitive to pHe and the buffer present. Exploiting this mechanism therapeutically may benefit patients with obesity.

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来源期刊
Obesity
Obesity 医学-内分泌学与代谢
CiteScore
11.70
自引率
1.40%
发文量
261
审稿时长
2-4 weeks
期刊介绍: Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.
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