The role of RGS9 in pancreatic islet function

尽管我们的能量摄入和消耗每天都在变化，但我们的血糖水平仍保持在一个狭窄的范围内，这依赖于位于胰腺的称为朗格汉斯胰岛的特殊细胞群分泌的激素。朗格汉斯人的胰岛由各种类型的细胞组成，包括分泌胰岛素的β细胞，胰岛素是一种负责降低餐后血糖的荷尔蒙。胰岛素的产生受到非常严格的控制，以便分泌的胰岛素恰好足以将血糖降到正常范围内，但又不能太多，这可能会引发非常危险的低血糖。因此，胰岛素的分泌是通过整合各种营养、神经和激素信号来严格调控的，其中很大一部分信号通过位于细胞膜上的蛋白质发挥作用，这种蛋白质被称为细胞表面受体。这些受体可以感知细胞外环境，并指示细胞做出相应的反应。我的NSERC资助的研究项目的长期目标是了解被称为“G蛋白信号调节因子”或RGS蛋白的蛋白质如何控制细胞表面受体的功能，以调节胰岛β细胞的功能和胰岛素的产生。在这个提案中，我们将利用分子工具和转基因小鼠模型，系统地研究RGS蛋白家族中的一个成员RGS9在形成朗格汉斯胰岛的细胞中的作用。参加该项目的本科生和研究生将获得代谢调节、激素释放和全动物生理学方面的多样化培训。我们期待这项研究的结果将为RGS9在β细胞中的作用和作用机制以及在调节胰岛素分泌方面提供重要的见解。

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.