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

Abstract 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 is...

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Autores principales:	Yanqing Zhang, Meifen Wu, Wynn Htun, Emily W. Dong, Franck Mauvais-Jarvis, Vivian A. Fonseca, Hongju Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88d07d8e9add4b2fa9564169da40f93b
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spelling	oai:doaj.org-article:88d07d8e9add4b2fa9564169da40f93b2021-12-02T12:32:21ZDifferential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors10.1038/s41598-017-08271-92045-2322https://doaj.org/article/88d07d8e9add4b2fa9564169da40f93b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08271-9https://doaj.org/toc/2045-2322Abstract 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.Yanqing ZhangMeifen WuWynn HtunEmily W. DongFranck Mauvais-JarvisVivian A. FonsecaHongju WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yanqing Zhang Meifen Wu Wynn Htun Emily W. Dong Franck Mauvais-Jarvis Vivian A. Fonseca Hongju Wu Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors
description	Abstract 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.
format	article
author	Yanqing Zhang Meifen Wu Wynn Htun Emily W. Dong Franck Mauvais-Jarvis Vivian A. Fonseca Hongju Wu
author_facet	Yanqing Zhang Meifen Wu Wynn Htun Emily W. Dong Franck Mauvais-Jarvis Vivian A. Fonseca Hongju Wu
author_sort	Yanqing Zhang
title	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_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_sort	differential effects of linagliptin on the function of human islets isolated from non-diabetic and diabetic donors
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/88d07d8e9add4b2fa9564169da40f93b
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Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors

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