肠胰高血糖素衍生肽在调节小鼠葡萄糖内稳态中是必不可少的。
Gut-Proglucagon-Derived Peptides Are Essential for Regulating Glucose Homeostasis in Mice.
机构信息
Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON M5G1X5, Canada; Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON M5G1X5, Canada.
出版信息
Cell Metab. 2019 Nov 5;30(5):976-986.e3. doi: 10.1016/j.cmet.2019.08.009. Epub 2019 Sep 5.
The importance of pancreatic versus intestinal-derived GLP-1 for glucose homeostasis is controversial. We detected active GLP-1 in the mouse and human pancreas, albeit at extremely low levels relative to glucagon. Accordingly, to elucidate the metabolic importance of intestinal proglucagon-derived peptides (PGDPs), we generated mice with reduction of Gcg expression within the distal (Gcg) or entire (Gcg) gut. Substantial reduction of gut Gcg expression markedly reduced circulating levels of GLP-1, and impaired glucose homeostasis, associated with increased levels of GIP, and accelerated gastric emptying. Gcg mice similarly exhibited lower circulating GLP-1 and impaired oral glucose tolerance. Nevertheless, plasma levels of insulin remained normal following glucose administration in the absence of gut-derived GLP-1. Collectively, our findings identify the essential importance of gut-derived PGDPs for maintaining levels of circulating GLP-1, control of gastric emptying, and glucose homeostasis.
胰腺和肠道来源的 GLP-1 对葡萄糖稳态的重要性存在争议。我们在小鼠和人类胰腺中检测到了活性 GLP-1，但相对于胰高血糖素而言，其水平极低。因此，为了阐明肠源前胰高血糖素衍生肽（PGDPs）的代谢重要性，我们生成了远端（Gcg）或整个（Gcg）肠道中 Gcg 表达减少的小鼠。肠道 Gcg 表达的大量减少显著降低了循环 GLP-1 水平，并损害了葡萄糖稳态，同时伴有 GIP 水平升高和胃排空加速。Gcg 小鼠同样表现出循环 GLP-1 水平降低和口服葡萄糖耐量受损。然而，在没有肠道来源的 GLP-1 的情况下，给予葡萄糖后，血浆胰岛素水平仍然正常。总之，我们的发现确定了肠道来源的 PGDPs 对于维持循环 GLP-1 水平、控制胃排空和葡萄糖稳态的至关重要性。
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