Molecular Mechanisms of Proglucagon Sorting to the Regulated Secretory Pathway

胰高血糖素原分选至调节分泌途径的分子机制

• 批准号: RGPIN-2016-04750
• 负责人: Dhanvantari, Savita
• 金额: $ 2.26万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630493
• 关键词: Molecular; Mechanisms; Proglucagon; Sorting; Regulated

Background: Peptide hormones are synthesized in the endoplasmic reticulum as larger precursors or prohormones, transported through the Golgi, and sorted to the secretory granules of the regulated secretory pathway. Within these granules, prohormones are processed to their constituent peptide hormones and stored until a stimulus triggers their release. Proglucagon is the precursor of the pancreatic hormone glucagon and the intestinal hormones, glucagon-like peptide (GLP)-1 and -2. These peptides must be stored in secretory granules in order to be secreted in response to nutrients. Glucagon, the major glucose counter-regulatory hormone, is secreted in response to low blood glucose levels in order to maintain euglycemia. Both GLP-1 and GLP-2 are secreted in response to nutrient ingestion; GLP-1 stimulates glucose-dependent insulin secretion, and GLP-2 increases intestinal blood flow and nutrient absorption. My research program focuses on identifying the molecular mechanisms by which proglucagon is directed to secretory granules.

背景：肽激素在内质网中合成为较大的前体或激素原，通过高尔基体运输，并分选至受调节的分泌途径的分泌颗粒。在这些颗粒内，激素原被加工成其组成肽激素并储存起来，直到刺激触发它们的释放。胰高血糖素原是胰腺激素胰高血糖素和肠道激素胰高血糖素样肽 (GLP)-1 和 -2 的前体。这些肽必须储存在分泌颗粒中，以便根据营养物质进行分泌。胰高血糖素是主要的葡萄糖反调节激素，是针对低血糖水平而分泌的，以维持血糖正常。 GLP-1 和 GLP-2 都会随着营养物质的摄入而分泌； GLP-1 刺激葡萄糖依赖性胰岛素分泌，GLP-2 增加肠道血流量和营养吸收。我的研究项目侧重于确定胰高血糖素原定向至分泌颗粒的分子机制。