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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688384
• 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.**

膳食脂肪是能量的重要来源和细胞的结构成分。然而，脂肪酸还具有调节能量平衡的信号作用。我的实验室致力于了解脂肪酸如何调节血糖（细胞的主要能量来源）。胰岛和细胞簇可以感知禁食和进食时血糖水平的变化，这些细胞将适当平衡的胰岛素和胰高血糖素激素释放到血流中。这些激素具有相反的作用，促进身体组织对糖的摄取（胰岛素）或释放（胰高血糖素），从而将血糖水平维持在较窄的范围内。脂肪酸在多个层面上影响血糖，影响胰岛激素分泌和糖摄取。在胰岛中，脂肪酸通过代谢或通过与细胞表面 G 蛋白偶联受体结合来发出信号。最近，G蛋白偶联受体Gpr120被发现可以介导脂肪酸对糖摄取的影响。我们提出的研究将扩展我们对脂肪酸调节胰岛功能的研究，深入了解 Gpr120 在胰岛素和胰高血糖素分泌、胰岛功能中的作用，以及最重要的是，它如何影响血糖水平。为了解决这个问题，我的实验室开发了一种独特的基因小鼠模型，结合我们在胰岛功能研究方面已有的专业知识，将使我们能够实现这一目标。我们将专门灭活小鼠体内产生胰岛素（胰腺的β细胞）或胰高血糖素（胰腺的α细胞）的细胞中编码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。我们将进一步鉴定 Gpr120 刺激后细胞内激活的信号。该研究计划将提供有关膳食脂肪如何调节两种对葡萄糖稳态至关重要的激素产生的关键信息，并揭示新型受体 Gpr120 在此过程中的作用和作用机制。 **