The role of RGS9 in pancreatic islet function

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The maintenance of our blood sugar levels within a narrow range despite daily variations in our energy intake and expenditure relies on hormones secreted by specialized groups of cells located in the pancreas called the islets of Langerhans. Islets of Langerhans are composed of various cell types including the beta-cell that secretes insulin, the hormone responsible for the lowering of our blood sugar after a meal. The production of insulin is very tightly controlled so as to secrete just enough to lower blood glucose within the normal range but not too much, which could trigger very dangerous hypoglycemia. Hence, insulin secretion is tightly regulated via the integration of a variety of nutrient, neural, and hormonal signals, a large proportion of which act through proteins that are located at the membrane of the cell, called cell-surface receptors. These receptors can sense the extracellular milieu and instruct the cell to respond accordingly. The long-term objective of my NSERC-funded research program is to understand how proteins called "Regulators of G protein Signaling", or RGS proteins, control the function of cell-surface receptors to regulate the function of pancreatic beta cells and the production of insulin. Using molecular tools and genetically modified mouse models, in this proposal we will systematically examine the role of one member of the RGS protein family, RGS9, in the cells that form the islets of Langerhans. Undergraduate and graduate students participating in this program will gain a diversified training in metabolic regulations, hormone release, and whole-animal physiology. We anticipate that the results of this research will provide important insights into the role and mechanism of action of RGS9 in the beta cell and in the regulation of insulin secretion.