Role of Neuronal Glucosensing in the Regulation of Energy Homeostasis

Abstract

Glucosensing is a property of specialized neurons in the brain that regulate their membrane potential and firing rate as a function of ambient glucose levels. These neurons have several similarities to β- and α-cells in the pancreas, which are also responsive to ambient glucose levels. Many use glucokinase as a rate-limiting step in the production of ATP and its effects on membrane potential and ion channel function to sense glucose. Glucosensing neurons are organized in an interconnected distributed network throughout the brain that also receives afferent neural input from glucosensors in the liver, carotid body, and small intestines. In addition to glucose, glucosensing neurons can use other metabolic substrates, hormones, and peptides to regulate their firing rate. Consequently, the output of these “metabolic sensing” neurons represents their integrated response to all of these simultaneous inputs. The efferents of these neurons regulate feeding, neuroendocrine and autonomic function, and thereby energy expenditure and storage. Thus, glucosensing neurons play a critical role in the regulation of energy homeostasis. Defects in the ability to sense glucose and regulatory hormones like leptin and insulin may underlie the predisposition of some individuals to develop diet-induced obesity.