Zinc-induced activation of GPR39 regulates glucose homeostasis through glucose-dependent insulinotropic polypeptide secretion from enteroendocrine K-cells.

Zinc-induced activation of GPR39 regulates glucose homeostasis through glucose-dependent insulinotropic polypeptide secretion from enteroendocrine K-cells. Biol Chem. 2018 Dec 01;: Authors: Moran BM, Miskelly MG, Abdel-Wahab YHA, Flatt PR, McKillop AM Abstract The role of Zn2+-sensing receptor GPR39 on glucose homeostasis and incretin regulation was assessed in enteroendocrine L- and K-cells. Anti-hyperglycaemic, insulinotropic and incretin secreting properties of Zn2+ were explored in normal, diabetic and incretin receptor knockout mice. Compared to intraperitoneal injection, oral administration of Zn2+ (50 μmol/kg body weight) with glucose (18 mmol/kg) in lean mice reduced the glycaemic excursion by 25-34% (p<0.05-p<0.001) and enhanced glucose-induced insulin release by 46-48% (p<0.05-p<0.01). In diabetic mice, orally administered Zn2+ lowered glucose by 24-31% (p<0.01) and augmented insulin release by 32% (p<0.01). In GLP-1 receptor knockout mice, Zn2+ reduced glucose by 15-28% (p<0.05-p<0.01) and increased insulin release by 35-43% (p<0.01). In contrast Zn2+ had no effect on responses of GIP receptor knockout mice. Consistent with this, Zn2+ had no effect on circulating total GLP-1 whereas GIP release was stimulated by 26% (p<0.05) in lean mice. Immunocytochemistry demonstrated GPR39 expression on mouse enteroendocrine L- and K-cells, GLUTag cells and pGIP/Neo STC-1 cells. Zn2+ had a direct effect o...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research