The role of GPR120 in glucose homeostasis.

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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.