GPR39, a Receptor of the Ghrelin Receptor Family, Plays a Role in the Regulation of Glucose Homeostasis in a Mouse Model of Early Onset Diet-Induced Obesity

作者：Pieter–Jan Verhulst, Anneleen Lintermans, Sara Janssen, Dirk Loeckx, Uwe Himmelreich, J. Buyse, Jan Tack, Inge Depoortere · 发表于：Journal of Neuroendocrinology · 年份：2011 · DOI：10.1111/j.1365-2826.2011.02132.x · 被引用次数：36 · 研究领域：Regulation of Appetite and Obesity、Biochemical Analysis and Sensing Techniques、Adipokines, Inflammation, and Metabolic Diseases

GPR39, which may function as a Zn(2+) sensor, is a member of the G protein-coupled receptor family that also includes the receptor for the hunger hormone ghrelin. The down-regulation of GPR39 mRNA in adipose tissue of obese type 2 diabetic patients suggests that GPR39 may contribute to the pathogenesis of the disease. The present study aimed to investigate the role of GPR39 in the regulation of energy balance and glucose homeostasis in wild-type (GPR39(+/+) ) and GPR39 knockout mice (GPR39(-/-) ) with obesity-related type 2 diabetes. GPR39 mRNA levels in adipose tissue of fasted GPR39(+/+) mice fed a high-fat diet (HFD) for 30 weeks were reduced and correlated positively with blood glucose levels. Body weight, fat percentage and energy intake were increased in the HFD group but did not differ between both genotypes. Within the HFD group, blood glucose levels were lower in GPR39(-/-) than in GPR39(+/+) mice, despite significant reductions in prandial plasma insulin levels. The latter may not be a result of changes in β-cell hyperplasia because immunohistochemical staining of pancreata of mice on a HFD showed no differences between genotypes. The lower blood glucose levels may involve alterations in insulin sensitivity as revealed by glucose tolerance tests and respiratory quotient measurements that showed a preference of obese GPR39(-/-) mice for the use of carbohydrates as metabolic fuel. The increase in plasma ghrelin levels in GPR39(-/-) mice fed a HFD may contribute to the...