期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 88, 期 4, 页码 351-358出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-009-0571-z
关键词
Glucagon-like peptide-1; Type 1 diabetes; Cell differentiation; beta cell regeneration; Intestinal stem cell
资金
- Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea [A062260]
- American Diabetes Association
To investigate whether the local production of glucagon-like peptide-1 (GLP-1) in the intestine can differentiate intestinal stem/progenitor cells into insulin-producing cells, we intra-intestinally injected a recombinant adenovirus expressing GLP-1 (rAd-GLP-1) into diabetic mice. There were no significant differences in body weight or food intake between rAd-GLP-1- and rAd-beta GAL-treated control mice. rAd-GLP-1-treated mice showed intestinal insulin mRNA expression, insulin- and glucagon-positive cells in the intestine, and significantly increased serum insulin, but not glucagon. rAd-GLP-1 injection significantly reduced blood glucose levels and improved glucose tolerance compared with controls. Expression of transcription factors related to beta cell differentiation, neurogenin3 (ngn3) and neurogenin differentiation factor (NeuroD), was detected in the intestine at 2 weeks after rAd-GLP-1 injection. We suggest that expression of GLP-1 in the intestine by intra-intestinal delivery of rAd-GLP-1 may induce differentiation of intestinal stem/progenitor cells into insulin-producing cells, mediated by ngn3 and NeuroD expression, contributing to lowered blood glucose levels in diabetic mice.
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