Molecular Mechanisms of Proglucagon Sorting to the Regulated Secretory Pathway

背景资料：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，并被分选到受调节的分泌途径的分泌颗粒。在这些颗粒中，激素原被加工成它们的组成肽激素并储存，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，以便响应于营养物而分泌。胰高血糖素是主要的葡萄糖反调节激素，其响应于低血糖水平而分泌，以维持正常血糖。GLP-1和GLP-2都是响应营养摄入而分泌的; GLP-1刺激葡萄糖依赖性胰岛素分泌，GLP-2增加肠血流量和营养吸收。我的研究项目集中于确定胰高血糖素原被定向为分泌颗粒的分子机制。

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.