Amelioration of hyperglycemia by intestinal overexpression of glucagon-like peptide-1 in mice.
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-betaGAL-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, neurogenin 3 (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.
Liu
Meng-Ju
MJ
Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Han
Jaeseok
J
Lee
Young-Sun
YS
Park
Mi-Sung
MS
Shin
Seungjin
S
Jun
Hee-Sook
HS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000628:therapy*; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000628:therapy*; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007422:Intestines / Q000166:cytology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors
D052216:Glucagon-Like Peptide 1