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A novel brain-to-pancreatic islet neural circuit regulates glucose homeostasis

一种新型脑-胰岛神经回路调节葡萄糖稳态

基本信息

批准号：
10886883
负责人：
Yanlin He
金额：
$ 21.3万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-24 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10886883
关键词：
Animals Area Blood Blood Glucose Brain Brain region Cell Nucleus Central Nervous System Data Defense Mechanisms Development Diabetes Mellitus Electrophysiology (science)Equilibrium Event Fiber Genetic Glucagon Glucose Glutamates Hormones Hyperglycemia Hypoglycemia Hypothalamic structure Impairment Insulin Insulin-Dependent Diabetes Mellitus Islets of Langerhans Knowledge Lateral Life Maintenance Maps Measures Molecular Target Monitor Mus Neural Pathways Neurons Obesity Outcome Pancreas Pathway interactions Photometry Physiological Play Population Prevention Process Regulation Role Testing Transgenic Mice Tyrosine 3-Monooxygenase Vagus nerve structure blood glucose regulation diabetic patient dorsal motor nucleus experimental study falls in vivo insulin secretion islet mouse model neural neural circuit neural network new therapeutic target novel novel therapeutic intervention optogenetics pancreatic islet function prevent raphe nucleus magnus response ventromedial hypothalamic nucleus vesicular GABA transporter

项目摘要

Project Summary Glucose-sensing neurons in the brain respond to glucose fall by altering their firing activities, which trigger the counterregulatory responses to prevent severe hypoglycemia. One essential process of the central nervous system in the maintenance of blood glucose levels is through the regulation of pancreatic islets. The ventromedial hypothalamus (VMH) is a critical component of neural networks that regulate blood glucose. Neurons express vesicular GABA transporter (Vgat) are concentrated in the ventrolateral part of VMH (vlVMH). We found that the majority of these VgatvlVMH neurons are glucose-inhibited (GI) neurons. Activation of these GI-VgatvlVMH neurons will reduce insulin secretion to increase blood glucose under hypoglycemia conditions. Following our pilot observations, we will combine neural circuits mapping, fiber photometry, electrophysiology, optogenetics, and chemogenetics to test the hypothesis that VgatvlVMH neurons regulates glucose homeostasis by changing insulin and glucagon secretion via the brain-to-pancreatic islet pathway. Aim 1 will establish the physiological functions of VgatvlVMH neurons in animals under different conditions (e.g. hyperglycemic, obesity, and diabetes) and further confirm their roles in regulating blood glucose levels. Aim 2 will determine if the VgatvlVMH-originated neural circuits contribute to glucose homeostasis via regulating pancreatic islet function. In aim 3, we will identify the VgatvlVMH neurons that regulate blood glucose via sympathetic pancreatic-projecting tyrosine hydroxylase (TH) neurons. The accomplishment of these studies may reveal the important functions of a novel brain-to-pancreatic islet neural circuit in regulating insulin secretion that has never been studied before. More importantly, we will delineate a new molecular target for glucose homeostasis, which may provide a framework for the development of novel therapeutic strategies for diabetes and obesity.

项目总结