Glucagon-like peptide-2 reduces intestinal permeability but does not modify the onset of type 1 diabetes in the nonobese diabetic mouse.
The development of type 1 diabetes (T1D) has been linked to environmental factors and dietary components. Increasing evidence indicates that the integrity of the gut mucosa plays a role in the development of autoimmune diseases, and evidence from both preclinical and clinical studies demonstrates that increased leakiness of the intestinal epithelium precedes the development of type 1 diabetes. However, there is limited information on modulation of gut barrier function and its relationship to diabetes development. Here we show that the nonobese diabetic (NOD) mouse, a model of T1D, exhibits enhanced intestinal transcellular permeability before the development of autoimmune diabetes. Treatment of NOD mice with a glucagon-like peptide 2 (GLP-2) analog, synthetic human [Gly(2)] glucagon-like peptide-2 (h[Gly(2)]GLP-2, increased the length and weight of the small bowel and significantly improved jejunal transepithelial resistance. However, chronic administration of once daily h[Gly(2)]GLP-2 failed to delay or reverse the onset of T1D when treatment was initiated in young, normoglycemic female NOD mice. Furthermore, h[Gly(2)]GLP-2 administration had no significant effect on lymphocyte subpopulations in NOD mice. These findings demonstrate that h[Gly(2)]GLP-2-mediated enhancement of gut barrier function in normoglycemic NOD mice disease is not sufficient to prevent or delay the development of experimental T1D.
Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Irene
I
Hadjiyanni
Kunmin Karen
KK
Li
Daniel J
DJ
Drucker
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology* / Q000627:therapeutic use*; D007107:Immune System / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D016688:Mice, Inbred NOD; D009929:Organ Size; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D010539:Permeability / Q000187:drug effects; D011236:Prediabetic State / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D053767:Glucagon-Like Peptide 2; D010455:Peptides; C494910:teduglutide