Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan; Division of Metabolism and Clinical Nutrition, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan.
Curr Opin Pharmacol. 2013 Dec;13(6):946-53. doi: 10.1016/j.coph.2013.09.013. Epub 2013 Oct 4.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are intestinal hormones secreted in response to ingestion of various nutrients. These incretins stimulate insulin secretion from pancreatic β cells in a glucose-dependent fashion. GIP and GLP-1 actions are mediated by specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which are expressed in pancreatic β cells and various other tissues and organs. Investigations using mice deficient in GIPR and/or GLP-1R have clarified roles of the incretins in enhancement of glucose-dependent insulin secretion from βcells as well as divergent biological activities with therapeutic implications for diabetes-related complications, such as cardiovascular diseases, retinopathy, nephropathy and neuropathy, and comorbidities, such as cognitive impairment, bone fracture and obesity. We review here recent findings on the extra-pancreatic effects of GIP and GLP-1 from the perspective of diabetes treatment.
葡萄糖依赖性胰岛素释放多肽（GIP）和胰高血糖素样肽-1（GLP-1）是响应各种营养物质摄入而分泌的肠激素。这些肠促胰岛素以葡萄糖依赖性的方式刺激胰腺β细胞分泌胰岛素。GIP 和 GLP-1 的作用是通过特定的受体介导的，即 GIP 受体（GIPR）和 GLP-1 受体（GLP-1R），它们在胰腺β细胞和其他各种组织和器官中表达。使用缺乏 GIPR 和/或 GLP-1R 的小鼠进行的研究阐明了肠促胰岛素在增强β细胞葡萄糖依赖性胰岛素分泌中的作用，以及具有治疗糖尿病相关并发症（如心血管疾病、视网膜病变、肾病和神经病变）和合并症（如认知障碍、骨折和肥胖症）的不同生物学活性。我们在此从糖尿病治疗的角度综述了 GIP 和 GLP-1 的胰腺外作用的最新发现。
