期刊
CELL METABOLISM
卷 30, 期 5, 页码 976-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2019.08.009
关键词
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资金
- Novo Nordisk
- Banting and Best Diabetes Center Chair in incretin biology
- CIHR Foundation grant [154321]
- BBDC
- Kangbuk Samsung Hospital
- NIDDK [RRID: SCR_014393, UC4 DK104211, DK108120, DK106755, DK20593]
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(DistalGut-/-)) or entire (Gcg(Gut-/-)) 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(DistalGut-/-) 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.
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