| Literature DB >> 31495689 |
Youngmi Song1, Jacqueline A Koehler2, Laurie L Baggio2, Alvin C Powers3, Darleen A Sandoval4, Daniel J Drucker5.
Abstract
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 (GcgDistalGut-/-) or entire (GcgGut-/-) 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. GcgDistalGut-/- 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.Entities:
Keywords: GIP; GLP-1; diabetes; enteroendocrine cell; glucagon; incretin; insulin; intestine; islet; pancreas
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Year: 2019 PMID： 31495689 PMCID： PMC8140521 DOI： 10.1016/j.cmet.2019.08.009
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287