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Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors

Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated is...

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Autores principales: Zhang, Yanqing, Wu, Meifen, Htun, Wynn, Dong, Emily W., Mauvais-Jarvis, Franck, Fonseca, Vivian A., Wu, Hongju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554162/
https://www.ncbi.nlm.nih.gov/pubmed/28801559
http://dx.doi.org/10.1038/s41598-017-08271-9
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author Zhang, Yanqing
Wu, Meifen
Htun, Wynn
Dong, Emily W.
Mauvais-Jarvis, Franck
Fonseca, Vivian A.
Wu, Hongju
author_facet Zhang, Yanqing
Wu, Meifen
Htun, Wynn
Dong, Emily W.
Mauvais-Jarvis, Franck
Fonseca, Vivian A.
Wu, Hongju
author_sort Zhang, Yanqing
collection PubMed
description Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment. Our data showed that linagliptin significantly improved glucose-stimulated insulin secretion for both non-diabetic and diabetic human islets, but its effectiveness on T2D islets was lower than on normal islets. The differential effects were attributed to reduced GLP-1 receptor expression in diabetic islets. In addition, linagliptin treatment increased the relative GLP-1 vs glucagon production in both non-diabetic and diabetic islets, suggesting a positive role of linagliptin in modulating α cell function to restore normoglycemia. Our study indicated that, from the standpoint of islet cell function, linagliptin would be more effective in treating early-stage diabetic patients before they develop severe β cell dysfunction.
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spelling pubmed-55541622017-08-15 Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors Zhang, Yanqing Wu, Meifen Htun, Wynn Dong, Emily W. Mauvais-Jarvis, Franck Fonseca, Vivian A. Wu, Hongju Sci Rep Article Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment. Our data showed that linagliptin significantly improved glucose-stimulated insulin secretion for both non-diabetic and diabetic human islets, but its effectiveness on T2D islets was lower than on normal islets. The differential effects were attributed to reduced GLP-1 receptor expression in diabetic islets. In addition, linagliptin treatment increased the relative GLP-1 vs glucagon production in both non-diabetic and diabetic islets, suggesting a positive role of linagliptin in modulating α cell function to restore normoglycemia. Our study indicated that, from the standpoint of islet cell function, linagliptin would be more effective in treating early-stage diabetic patients before they develop severe β cell dysfunction. Nature Publishing Group UK 2017-08-11 /pmc/articles/PMC5554162/ /pubmed/28801559 http://dx.doi.org/10.1038/s41598-017-08271-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Yanqing
Wu, Meifen
Htun, Wynn
Dong, Emily W.
Mauvais-Jarvis, Franck
Fonseca, Vivian A.
Wu, Hongju
Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors
title Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors
title_full Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors
title_fullStr Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors
title_full_unstemmed Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors
title_short Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors
title_sort differential effects of linagliptin on the function of human islets isolated from non-diabetic and diabetic donors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554162/
https://www.ncbi.nlm.nih.gov/pubmed/28801559
http://dx.doi.org/10.1038/s41598-017-08271-9
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