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

作者：Zhang, Yanqing; Wu, Meifen; Htun, Wynn; Dong, Emily W.; Mauvais-Jarvis, Franck; Fonseca, Vivian A.; Wu, Hongju^*

来源：Scientific Reports, 2017, 7(1): 7964.

DOI：10.1038/s41598-017-08271-9

• GLUCAGON-LIKE PEPTIDE-1
• BETA-CELL FUNCTION
• DIPEPTIDYL PEPTIDASE-4 INHIBITOR
• GENE-TRANSFER
• DB/DB MICE
• GLP-1
• HYPOGLYCEMIA
• SECRETION
• RESPONSES
• PANCREAS

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 beta cell function using animal models and isolated islets from normal subjects. Since beta 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 alpha 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 beta cell dysfunction.

• 出版日期2017-8-11
• 单位广东医科大学