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β 细胞 GLP-1R 信号在小鼠垂直袖状胃切除术后改变 α 细胞前胰高血糖素加工。

β Cell GLP-1R Signaling Alters α Cell Proglucagon Processing after Vertical Sleeve Gastrectomy in Mice.

机构信息

Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.

Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.

出版信息

Cell Rep. 2018 Apr 24;23(4):967-973. doi: 10.1016/j.celrep.2018.03.120.

DOI:10.1016/j.celrep.2018.03.120
PMID:29694904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5983903/
Abstract

Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes high rates of type 2 diabetes remission and remarkable increases in postprandial glucagon-like peptide-1 (GLP-1) secretion. GLP-1 plays a critical role in islet function by potentiating glucose-stimulated insulin secretion; however, the mechanisms remain incompletely defined. Therefore, we applied a murine VSG model to an inducible β cell-specific GLP-1 receptor (GLP-1R) knockout mouse model to investigate the role of the β cell GLP-1R in islet function. Our data show that loss of β cell GLP-1R signaling decreases α cell GLP-1 expression after VSG. Furthermore, we find a β cell GLP-1R-dependent increase in α cell expression of the prohormone convertase required for the production of GLP-1 after VSG. Together, the findings herein reveal two concepts. First, our data support a paracrine role for α cell-derived GLP-1 in the metabolic benefits observed after VSG. Second, we have identified a role for the β cell GLP-1R as a regulator of α cell proglucagon processing.

摘要

减重手术，如垂直袖状胃切除术（VSG），可导致 2 型糖尿病缓解率高，并显著增加餐后胰高血糖素样肽-1（GLP-1）的分泌。GLP-1 通过增强葡萄糖刺激的胰岛素分泌在胰岛功能中发挥关键作用；然而，其机制仍不完全明确。因此，我们应用了一种小鼠 VSG 模型到诱导型β细胞特异性 GLP-1 受体（GLP-1R）敲除小鼠模型，以研究β细胞 GLP-1R 在胰岛功能中的作用。我们的数据表明，β细胞 GLP-1R 信号的丧失会降低 VSG 后α细胞 GLP-1 的表达。此外，我们发现 VSG 后β细胞 GLP-1R 依赖性增加了 GLP-1 产生所需的前激素转化酶在α细胞中的表达。综上所述，这些发现揭示了两个概念。首先，我们的数据支持了α细胞衍生的 GLP-1 在 VSG 后观察到的代谢益处中的旁分泌作用。其次，我们已经确定了β细胞 GLP-1R 作为调节α细胞前胰高血糖素加工的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/907cb12c947b/nihms966399f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/dc9632335477/nihms966399f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/21016e344dc7/nihms966399f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/0cf98120d734/nihms966399f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/907cb12c947b/nihms966399f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/dc9632335477/nihms966399f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/21016e344dc7/nihms966399f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/0cf98120d734/nihms966399f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/5983903/907cb12c947b/nihms966399f4.jpg

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Endocrinology. 2017 Dec 1;158(12):4139-4151. doi: 10.1210/en.2017-00564.
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Why is it so difficult to measure glucagon-like peptide-1 in a mouse?为什么在老鼠体内检测胰高血糖素样肽-1 如此困难？
Diabetologia. 2017 Oct;60(10):2066-2075. doi: 10.1007/s00125-017-4347-7. Epub 2017 Jul 1.
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Impact of the Glucagon Assay When Assessing the Effect of Chronic Liraglutide Therapy on Glucagon Secretion.评估慢性利拉鲁肽治疗对胰高血糖素分泌影响时检测胰高血糖素的作用。
14-3-3 是否是解锁改善代谢稳态和β细胞功能的新途径的组合？
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Berberine enhances the function of db/db mice islet β cell through GLP-1/GLP-1R/PKA signaling pathway in intestinal L cell and islet α cell.小檗碱通过肠道L细胞和胰岛α细胞中的GLP-1/GLP-1R/PKA信号通路增强db/db小鼠胰岛β细胞的功能。
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Bariatric Surgery: Targeting pancreatic β cells to treat type II diabetes.减重手术：针对胰腺β细胞治疗 2 型糖尿病。
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