| Impact of the Dipeptidyl Peptidase-4 Inhibitor Vildagliptin on Glucose Tolerance and β-Cell Function and Mass in Insulin Receptor Substrate-2-Knockout Mice Fed a High-Fat Diet. | |
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MedLine Citation:
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PMID: 22315446 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Type 2 diabetes is characterized by diminished pancreatic β-cell mass and function. Glucagon-like peptide-1 has been reported to increase islet cell proliferation and reduce apoptosis of β-cells in rodents. In this study, we explored the effect of chronic administration of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance, β-cell function, and β-cell mass in Irs2-knockout (Irs2(-/-)) mice. Wild-type and Irs2(-/-) mice were fed a high-fat diet for 20 wk, with or without vildagliptin. In both genotypes of mice, vildagliptin significantly decreased the area under the curve (0-120 min) of blood glucose and increased the insulin response to glucose during the oral glucose tolerance test. In the oral glucose tolerance test performed 1 d after discontinuation of vildagliptin administration, the area under the curve (0-120 min) of blood glucose was still significantly decreased and the insulin response to glucose was significantly increased in the Irs2(-/-) mice treated with vildagliptin as compared with the values in the mice not treated with vildagliptin. Histochemical analysis of the pancreatic islets revealed significant increase of the β-cell mass and decrease in the proportion of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive β-cells but no significant increase of the bromodeoxyuridine incorporation in Irs2(-/-) mice treated with vildagliptin. Our results suggest that vildagliptin improved glucose tolerance and increased the β-cell mass by reducing β-cell apoptosis in the Irs2(-/-) mice, and that the reduction of β-cell apoptosis by vildagliptin was independent of the Irs2 expression in the cells. |
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Authors:
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Koichiro Sato; Akinobu Nakamura; Jun Shirakawa; Tomonori Muraoka; Yu Togashi; Kazuaki Shinoda; Kazuki Orime; Naoto Kubota; Takashi Kadowaki; Yasuo Terauchi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-7 |
Journal Detail:
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Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Endocrinology and Metabolism (K.S., A.N., J.S., T.M., Y.To., K.S., K.O., Y.Te.), Graduate School of Medicine, Yokohama City University, Japan; and Department of Diabetes and Metabolic Diseases (N.K., T.K.), Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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