Advertisement

 

 

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

Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors.
Author Information (click to view)

Zhang Y, Wu M, Htun W, Dong EW, Mauvais-Jarvis F, Fonseca VA, Wu H,


Zhang Y, Wu M, Htun W, Dong EW, Mauvais-Jarvis F, Fonseca VA, Wu H, (click to view)

Zhang Y, Wu M, Htun W, Dong EW, Mauvais-Jarvis F, Fonseca VA, Wu H,

Advertisement

Scientific reports 2017 08 117(1) 7964 doi 10.1038/s41598-017-08271-9
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.

Submit a Comment

Your email address will not be published. Required fields are marked *

2 × four =

[ HIDE/SHOW ]