The role of GPR120 in glucose homeostasis.

GPR120 在葡萄糖稳态中的作用。

• 批准号: RGPIN-2016-03952
• 负责人: Poitout, Vincent
• 金额: $ 2.99万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=707940
• 关键词: role; GPR120; glucose; homeostasis.

Dietary fats are an important source of energy and structural component of the cell. However, fatty acids also serve a signalling role regulating energy balance. My lab endeavors to understand how fatty acids regulate blood sugar, the primary source of energy for the cell. Changes in blood sugar levels upon fasting and feeding are sensed by pancreatic islets, clusters of cells which release an appropriate balance of the hormones insulin and glucagon into the blood stream. These hormones have opposite actions promoting the uptake (insulin) or release (glucagon) of sugar by body tissue maintaining blood sugar levels in a narrow range. Fatty acids impact blood sugar at multiple levels affecting islet hormone secretion as well as sugar uptake. In islets, fatty acids signal either through metabolism or by binding to cell surface G-protein coupled receptors. Recently, the G-protein coupled receptor, Gpr120, was found to mediate the effects of fatty acids on sugar uptake. Our proposed research will extend our investigation into the regulation of islet function by fatty acids providing insight into the role of Gpr120 in insulin and glucagon secretion, islet function and, most importantly, how this impacts blood sugar levels. To address this, my lab has developed a unique genetic mouse model that, combined with our established expertise in the study of islet function, will allow us to achieve this objective. We will specifically inactivate the gene encoding for Gpr120 in cells that produce insulin (the beta cells of the pancreas) or glucagon (the alpha cells of the pancreas) in mice. We will ascertain the impact of these gene deletions on hormone production and glucose homeostasis. We will further identify the signals that are activated within the cells upon stimulation of Gpr120. This research program will provide key information on how dietary fat regulate the production of two hormones that are essential for glucose homeostasis, and unravel the role and mechanism of action of the novel receptor Gpr120 in this process.

饮食脂肪是细胞的能量和结构成分的重要来源。但是，脂肪酸还具有调节能量平衡的信号传导作用。我的实验室努力了解脂肪酸如何调节血糖，这是细胞的主要能源。禁食和喂养时血糖水平的变化是通过胰岛，细胞的簇感测，这些细胞簇释放了胰岛素胰岛素和胰高血糖素的适当平衡。这些激素具有相反的作用，促进了人体组织促进糖的摄取（胰岛素）或释放（胰高血糖素），从而使血糖水平保持在狭窄的范围内。脂肪酸在影响胰岛激素分泌以及摄入糖的多个水平上影响血糖。在胰岛中，脂肪酸通过代谢或与细胞表面G蛋白偶联受体结合信号。最近，发现G蛋白偶联受体GPR120可以介导脂肪酸对糖摄取的影响。我们提出的研究将通过脂肪酸来扩展对胰岛功能调节的研究，从而洞悉GPR120在胰岛素和胰高血糖素分泌，胰岛功能，最重要的是，这如何影响血糖水平。为了解决这个问题，我的实验室开发了一种独特的遗传小鼠模型，该模型与我们在胰岛功能研究中既定的专业知识相结合，将使我们能够实现这一目标。我们将在产生胰岛素（胰腺的β细胞）或胰高血糖素（胰腺的α细胞）中的细胞中特异性灭活GPR120的基因。我们将确定这些基因缺失对激素产生和葡萄糖稳态的影响。我们将进一步确定刺激GPR120后在细胞中激活的信号。该研究计划将提供有关饮食脂肪如何调节两种激素的产生的关键信息，这些激素对葡萄糖稳态至关重要，并揭示了新型受体GPR120在此过程中的作用和机理。