Gut-Proglucagon-Derived Peptides Are Essential for Regulating Glucose Homeostasis in Mice.

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 (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 insu

SUBMITTER: Song Y 

PROVIDER: S-EPMC8140521 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature