The role of GPR120 in glucose homeostasis.

膳食脂肪是细胞的重要能量来源和结构成分。然而，脂肪酸也起到了调节能量平衡的信号作用。我的实验室努力了解脂肪酸是如何调节血糖的，血糖是细胞的主要能量来源。禁食和进食时血糖水平的变化是由胰岛感受到的，胰岛是一群细胞，它向血液中释放适当平衡的胰岛素和胰升糖素。这些激素具有相反的作用，促进身体组织对糖的吸收(胰岛素)或释放(胰高血糖素)，将血糖水平维持在一个狭窄的范围内。脂肪酸在多个水平上影响血糖，影响胰岛激素的分泌和糖的吸收。在胰岛，脂肪酸通过新陈代谢或通过与细胞表面G蛋白偶联受体结合来传递信号。最近，G蛋白偶联受体Gpr120被发现介导脂肪酸对糖吸收的影响。我们拟议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在胰岛素和胰升糖素分泌中的作用，胰岛功能，以及最重要的是，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，结合我们在胰岛功能研究方面的成熟专业知识，将使我们能够实现这一目标。我们将在小鼠分泌胰岛素(胰腺的β细胞)或胰升糖素(胰腺的α细胞)的细胞中特异地灭活编码Gpr120的基因。我们将确定这些基因缺失对激素产生和葡萄糖动态平衡的影响。我们将进一步确定Gpr120刺激后在细胞内激活的信号。这项研究计划将提供关于饮食脂肪如何调节两种激素的产生的关键信息，这两种激素是葡萄糖稳态所必需的，并揭示新型受体Gpr120在这一过程中的作用和作用机制。

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.