中国药科大学最新Cell子刊论文：揭开对抗低血糖的脑-肝神经回路

Core Viewpoint - The research published by a team from China Pharmaceutical University reveals a novel brain-liver neurocircuit involving VMH Galnt2 neurons that counterregulate hypoglycemia by increasing hepatic glucose production, providing new insights into the mechanisms of hypoglycemia resistance and potential innovative treatment strategies for metabolic diseases related to glucose regulation [3][7]. Summary by Sections Research Findings - The study identifies a biphasic pattern of glucose dynamics in the blood and hypothalamus during prolonged fasting, highlighting an additional threshold-dependent counterregulatory mechanism [4]. - This mechanism is mediated by a neural pathway from the ventromedial hypothalamus (VMH) to the paraventricular nucleus (PVH), then to the lateral paragigantocellular nucleus (LPGi), and finally to the liver, which detects neuroglycopenic states and activates sympathetic signals to drive hepatic glucose production [4]. Key Highlights - The biphasic model explains the counterregulatory response to hypoglycemia [5]. - VMH glucose-inhibitory neurons play a critical functional role in sensing neuroglycopenia [5]. - The brain-liver neural circuit emphasizes the counterregulatory response to hypoglycemia [5]. - Galnt2 serves as both a genetic marker and a molecular brake for VMH glucose-inhibitory neurons, regulating the glucose sensing threshold and metabolic homeostasis [5]. Implications - The study underscores a brain-liver neural pathway originating from VMH Galnt2 neurons that can sense and counterregulate hypoglycemia, potentially guiding the development of innovative treatment strategies for metabolic diseases characterized by abnormal glucose regulation [7].