Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells.
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.
Suzuki
Atsushi
A
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Nakauchi
Hiromitsu
H
Taniguchi
Hideki
H
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007328:Insulin / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000502:physiology*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D007328:Insulin; D010455:Peptides; D004763:Glucagon-Like Peptides; C055968:glucagon-like peptide 1 (1-37); D052216:Glucagon-Like Peptide 1; D005934:Glucagon