Glucagon and insulin act cooperatively in the regulation of prandial hepatic glycogen metabolism

胰高血糖素和胰岛素协同调节膳食肝糖原代谢

基本信息

批准号：
10668450
负责人：
Megan Capozzi
金额：
$ 1.83万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2023-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10668450
关键词：
Amino Acids Anabolism Attention Automobile Driving B-Lymphocytes Beta Cell Blood Glucose Bypass Carbon Cells Circulation Consensus Data Development Fasting Fatty Acids Foundations GLP-I receptor Glucagon Gluconeogenesis Glucose Glycogen Hepatic Hepatocyte Homeostasis Hormones Human Hypoglycemia Individual Ingestion Insulin Islets of Langerhans Liver Liver Glycogen Maintenance Mass Spectrum Analysis Measures Mediating Metabolic Metabolic Diseases Modeling Mus Nutrient Obesity Pancreatic Hormones Peripheral Physiological Plasma Regulation Research Personnel Rodent Role Signal Pathway Signal Transduction Stimulus Testing Tissues Tracer Work blood glucose regulation career feeding genetic manipulation glucose metabolism glucose tolerance glucose uptake glycemic control glycogen metabolism glycogenolysis insight insulin secretion insulin signaling islet liver metabolism mouse model new therapeutic target phosphoproteomics prevent response

项目摘要

Project Summary Glucagon and insulin are pancreatic hormones that control the glycemic response to fasting and feeding. Canonically, glucagon is secreted in the fasted state where it stimulates hepatic glycogenolysis and gluconeogenesis in order to raise glycemia. Conversely, insulin is secreted in response to elevated blood glucose to stimulate glucose uptake in peripheral tissues. These canonical, opposing effects of glucagon and insulin on the liver overlook the long understanding that amino acids in mixed nutrient feeding stimulate the islet a-cell to secrete glucagon. Moreover, our recent work has shown the importance of glucagon-stimulated insulin secretion to maintaining glucose tolerance. Therefore, the expected response to a physiologic mixed nutrient meal is the co-secretion of glucagon and insulin into portal circulation. The preliminary data presented herein support the notion that glucagon and insulin work cooperatively, not antagonistically, to control prandial glucose metabolism. We hypothesize that glucagon and insulin co-secretion controls hepatic glucose metabolism to allow glucose to reach the periphery before being stored in the liver. Successful completion of this project will alter our fundamental understanding of hepatic glucose metabolism and my provide insight for novel therapeutic targets for the treatment of metabolic disease. Importantly, completion of the proposed aims will support several new technical and conceptual developments that will provide a foundation for a career as an independent investigator.

项目摘要胰高血糖素和胰岛素是控制对禁食和饲料的血糖反应的胰腺激素。从规范上讲，胰高血糖素在禁食状态下分泌，在禁食状态下它刺激肝糖基解体和糖生成是为了提高血糖。相反，胰岛素是为了响应升高的血糖而分泌刺激周围组织中的葡萄糖摄取。这些规范的，胰岛素和胰岛素对肝脏忽略了较长的理解，即混合营养喂养中的氨基酸会刺激胰岛A细胞到分泌胰高血糖素。此外，我们最近的工作表明了胰高血糖素刺激的胰岛素分泌的重要性维持葡萄糖耐受性。因此，对生理混合营养餐的预期反应是将胰高血糖素和胰岛素共归化为门户循环。本文提供的初步数据支持胰高血糖素和胰岛素合作起作用而不是拮抗作用以控制挥助念珠葡萄糖代谢。我们假设胰高血糖素和胰岛素共泌液控制控制肝葡萄糖代谢，使葡萄糖达到在存放在肝脏中之前，到达外围。成功完成该项目将改变我们的对肝葡萄糖代谢的基本理解，我为新型治疗靶标提供了见识用于治疗代谢疾病。重要的是，提议的目标的完成将支持几个新的技术和概念的发展将为作为独立研究者的职业提供基础。