Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells

Atsushi Suzuki, Hiromitsu Nakauchi, Hideki Taniguchi

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Glucagon-like peptide (GLP) 1 is produced through posttranslational processing of proglucagon and acts as a regulator of various homeostatic events. Among its analogs, however, the function of GLP-1-(1-37), synthesized in small amounts in the pancreas, has been unclear. Here, we find that GLP-1-(1-37) induces insulin production in developing and, to a lesser extent, adult intestinal epithelial cells in vitro and in vivo, a process mediated by up-regulation of the Notch-related gene ngn3 and its downstream targets, which are involved in pancreatic endocrine differentiation. These cells became responsive to glucose challenge in vitro and reverse insulin-dependent diabetes after implantation into diabetic mice. Our findings suggest that efficient induction of insulin production in intestinal epithelial cells by GLP-1-(1-37) could represent a new therapeutic approach to diabetes mellitus.

Original languageEnglish
Pages (from-to)5034-5039
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number9
DOIs
Publication statusPublished - Apr 29 2003

All Science Journal Classification (ASJC) codes

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