GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis
GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis
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DOI：
10.1677/joe-08-0453
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发表时间：
2009-05-01
影响因子：
4
通讯作者：
Kowalski, Timothy J.
中科院分区：
文献类型：
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作者：
Lan, Hong;Vassileva, Galya;Kowalski, Timothy J.
G蛋白偶联受体119(GPR119)表达于胰岛和肠道，参与胰岛素和胰岛素的释放。据报道，GPR119基因敲除(GPR119(-/-))小鼠的胰岛形态正常，大小、体重(BW)和进食/禁食血糖水平也正常。然而，GPR119的生理功能及其在代谢应激下维持血糖稳态中的作用仍不清楚。在这里，我们报告了在基础和高脂饮食(HFD)诱导的肥胖下，独立产生的GPR119(-/-)NICE的表型。在低脂饮食喂养下，GPR119(-/-)小鼠的血糖和血脂正常，但体重指数和餐后活性胰高血糖素样肽1(GLP-1)水平较低。GPR119(-/-)小鼠营养刺激的GLP-1释放减弱，提示GPR119在GLP-1的生理调节中发挥作用。分泌物。在HFD喂养下，GPR119(+/+)和GPR119(-/-)小鼠体重增加相似，出现高胰岛素血症和高瘦素血症，但不出现高血糖或血脂异常。糖耐量和胰岛素耐量测试没有发现基因差异。这些数据表明，GPR119不是维持葡萄糖稳态所必需的。此外，我们发现作为GPR119配体的油酰乙醇胺(OEA)能够抑制GPR119(+/+)和GPR119(-/-)小鼠的摄食，这表明GPR119不是OEA低噬作用所必需的。我们的结果表明，GPR119对胰岛素和胰岛素的分泌很重要，但对食欲抑制没有影响。内分泌学杂志(2009)201,219-230
G protein-coupled receptor 119 (GPR119) is expressed in pancreatic islets and intestine, and is involved in insulin and incretin hormone release. GPR119-knockout (Gpr119(-/-)) mice were reported to have normal islet morphology and normal size, body weight (BW), and fed/fasted glucose levels. However, the physiological function of GPR119 and its role in maintaining glucose homeostasis under metabolic stress remain unknown. Here, we report the phenotypes of an independently generated line of Gpr119(-/-) nice under basal and high-fat diet (HFD)-induced obesity. Under low-fat diet feeding, Gpr119(-/-) mice show normal plasma glucose and lipids, but have lower BWs and lower post-prandial levels of active glucagon-like peptide 1 (GLP-1). Nutrient-stimulated GLP-1 release is attenuated in Gpr119(-/-) mice, suggesting that GPR119 plays a role in physiological regulation of GLP-1. secretion. Under HFD-feeding, both Gpr119(+/+) and Gpr119(-/-) mice gain weight similarly, develop hyperinsulinemia and hyperleptinemia, but not hyperglycemia or dyslipidemia. Glucose and insulin tolerance tests did not reveal a genotypic difference. These data show that GPR119 is not essential for the maintenance of glucose homeostasis. Moreover, we found that oleoylethanolamide (OEA), reported as a ligand for GPR119, was able to suppress food intake in both Gpr119(+/+) and Gpr119(-/-) mice, indicating that GPR119 is not required for the hypophagic effect of OEA. Our results demonstrate that GPR119 is important for incretin and insulin secretion, but not for appetite suppression. journal of Endocrinology (2009) 201, 219-230