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Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice
OBJECTIVE—Glucagon-like peptide-1 (GLP-1) and gastrin promote pancreatic β-cell function, survival, and growth. Here, we investigated whether GLP-1 and gastrin can restore the β-cell mass and reverse hyperglycemia in NOD mice with autoimmune diabetes. RESEARCH DESIGN AND METHODS—Acutely diabetic NOD...
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2584134/ https://www.ncbi.nlm.nih.gov/pubmed/18835930 http://dx.doi.org/10.2337/db08-0688 |
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author | Suarez-Pinzon, Wilma L. Power, Robert F. Yan, Yanhua Wasserfall, Clive Atkinson, Mark Rabinovitch, Alex |
author_facet | Suarez-Pinzon, Wilma L. Power, Robert F. Yan, Yanhua Wasserfall, Clive Atkinson, Mark Rabinovitch, Alex |
author_sort | Suarez-Pinzon, Wilma L. |
collection | PubMed |
description | OBJECTIVE—Glucagon-like peptide-1 (GLP-1) and gastrin promote pancreatic β-cell function, survival, and growth. Here, we investigated whether GLP-1 and gastrin can restore the β-cell mass and reverse hyperglycemia in NOD mice with autoimmune diabetes. RESEARCH DESIGN AND METHODS—Acutely diabetic NOD mice were treated with GLP-1 and gastrin, separately or together, twice daily for 3 weeks. Blood glucose was measured weekly and for a further 5 weeks after treatments, after which pancreatic insulin content and β-cell mass, proliferation, neogenesis, and apoptosis were measured. Insulin autoantibodies were measured, and adoptive transfer of diabetes and syngeneic islet transplant studies were done to evaluate the effects of GLP-1 and gastrin treatment on autoimmunity. RESULTS—Combination therapy with GLP-1 and gastrin, but not with GLP-1 or gastrin alone, restored normoglycemia in diabetic NOD mice. The GLP-1 and gastrin combination increased pancreatic insulin content, β-cell mass, and insulin-positive cells in pancreatic ducts, and β-cell apoptosis was decreased. Insulin autoantibodies were reduced in GLP-1–and gastrin-treated NOD mice, and splenocytes from these mice delayed adoptive transfer of diabetes in NOD-scid mice. Syngeneic islet grafts in GLP-1–and gastrin-treated NOD mice were infiltrated by leukocytes with a shift in cytokine expression from interferon-γ to transforming growth factor-β1, and β-cells were protected from apoptosis. CONCLUSIONS—Combination therapy with GLP-1 and gastrin restores normoglycemia in diabetic NOD mice by increasing the pancreatic β-cell mass and downregulating the autoimmune response. |
format | Text |
id | pubmed-2584134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-25841342009-12-01 Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice Suarez-Pinzon, Wilma L. Power, Robert F. Yan, Yanhua Wasserfall, Clive Atkinson, Mark Rabinovitch, Alex Diabetes Islet Studies OBJECTIVE—Glucagon-like peptide-1 (GLP-1) and gastrin promote pancreatic β-cell function, survival, and growth. Here, we investigated whether GLP-1 and gastrin can restore the β-cell mass and reverse hyperglycemia in NOD mice with autoimmune diabetes. RESEARCH DESIGN AND METHODS—Acutely diabetic NOD mice were treated with GLP-1 and gastrin, separately or together, twice daily for 3 weeks. Blood glucose was measured weekly and for a further 5 weeks after treatments, after which pancreatic insulin content and β-cell mass, proliferation, neogenesis, and apoptosis were measured. Insulin autoantibodies were measured, and adoptive transfer of diabetes and syngeneic islet transplant studies were done to evaluate the effects of GLP-1 and gastrin treatment on autoimmunity. RESULTS—Combination therapy with GLP-1 and gastrin, but not with GLP-1 or gastrin alone, restored normoglycemia in diabetic NOD mice. The GLP-1 and gastrin combination increased pancreatic insulin content, β-cell mass, and insulin-positive cells in pancreatic ducts, and β-cell apoptosis was decreased. Insulin autoantibodies were reduced in GLP-1–and gastrin-treated NOD mice, and splenocytes from these mice delayed adoptive transfer of diabetes in NOD-scid mice. Syngeneic islet grafts in GLP-1–and gastrin-treated NOD mice were infiltrated by leukocytes with a shift in cytokine expression from interferon-γ to transforming growth factor-β1, and β-cells were protected from apoptosis. CONCLUSIONS—Combination therapy with GLP-1 and gastrin restores normoglycemia in diabetic NOD mice by increasing the pancreatic β-cell mass and downregulating the autoimmune response. American Diabetes Association 2008-12 /pmc/articles/PMC2584134/ /pubmed/18835930 http://dx.doi.org/10.2337/db08-0688 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Islet Studies Suarez-Pinzon, Wilma L. Power, Robert F. Yan, Yanhua Wasserfall, Clive Atkinson, Mark Rabinovitch, Alex Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice |
title | Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice |
title_full | Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice |
title_fullStr | Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice |
title_full_unstemmed | Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice |
title_short | Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice |
title_sort | combination therapy with glucagon-like peptide-1 and gastrin restores normoglycemia in diabetic nod mice |
topic | Islet Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2584134/ https://www.ncbi.nlm.nih.gov/pubmed/18835930 http://dx.doi.org/10.2337/db08-0688 |
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