The insulin secretion in the pancreatic beta-cell under influence of different cannabinoid receptors and endocannabinoid metabolism

不同大麻素受体和内源性大麻素代谢影响下胰腺β细胞的胰岛素分泌

• 批准号: 386330389
• 负责人: Privatdozentin Dr. Ivonne Bazwinsky-Wutschke
• 金额: --
• 依托单位: Institut für Anatomie und Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/386330389?language=en
• 关键词: insulin; secretion; pancreatic; beta; cell

The endocannabinoid system (ECS) consisted of cannabinoid receptors, enzymes for the synthesis and degradation and endogenous ligands, the so called endocannabinoids. The ECS influences neuronal signaling, as well as hormonal secretion of the pancreatic islet. The endocannabinoid system affects the activity of pancreatic beta-cells by modulation of insulin secretion. Different cannabinoid receptors coupled to intracellular signaling pathways mediate effects of endocannabinoids. However, little is known about the second messengers associated with these pathways.In the proposal we plan to the following aspects by using the well-established rat insulinoma beta beta cell model INS-1 and a newly characterized human beta cell model EndoC-betaH1, genetically modified variants of EndoC-betaH1, isolated human pancreatic islets and cannabinoid receptor knockout mice. We will focus on: (1) Participation of ECS on modulation of physiologically or diabetic stimulated insulin secretion, while simultaneously investigating the signaling components involved, and (2) the importance of endocannabinoid metabolism and the receptor alterations for regulating insulin secretion and type 2 diabetes.Prospectively, the proposed study might contribute to our knowledge of the impact of G-protein-coupled receptor signaling pathways in pancreatic islets and will shed new light on the role of the ECS for the insulin secretion. Actively influencing the ECS opens new options for the treatment of the clinically highly relevant disease of type 2 diabetes.

内源性大麻素系统（ECS）由大麻素受体、合成和降解酶以及内源性配体组成，即内源性大麻素。ECS影响神经元信号传导以及胰岛的激素分泌。内源性大麻素系统通过调节胰岛素分泌来影响胰腺β细胞的活性。不同的大麻素受体偶联到细胞内信号传导途径介导内源性大麻素的作用。本研究计划利用已建立的大鼠胰岛β细胞模型INS-1和新近鉴定的人胰岛β细胞模型EndoC-betaH 1、EndoC-betaH 1的基因修饰变体、人胰岛和大麻素受体敲除小鼠，从以下几个方面进行研究。我们将重点关注：（1）ECS对生理或糖尿病刺激的胰岛素分泌的调节的参与，同时研究所涉及的信号传导组分，和（2）内源性大麻素代谢和受体改变对于调节胰岛素分泌和2型糖尿病的重要性。这项研究可能有助于我们了解G蛋白的影响，偶联胰岛中的受体信号通路，并将为ECS在胰岛素分泌中的作用提供新的线索。积极影响ECS为治疗临床高度相关的2型糖尿病开辟了新的选择。