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.
Hadjiyanni
Irene
I
Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Li
Kunmin Karen
KK
Drucker
Daniel J
DJ
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