CNS Regulation of Glucose Homeostasis: Role of the Leptin-Melanocortin System

AbstractPurpose of ReviewIn this brief review, we highlight studies that have contributed to our current understanding of glucose homeostasis by the central nervous system (CNS) leptin-melanocortin system, particularly proopiomelanocortin neurons and melanocortin-4 receptors (MC4R).Recent FindingsLeptin deficiency is associated with insulin resistance and impaired glucose metabolism whereas leptin administration improves tissue glucose uptake/oxidation and reduces hepatic glucose output. These antidiabetic effects of leptin have been demonstrated in experimental animals and humans, even when circulating insulin levels are barely detectable. Recent evidence suggests that these antidiabetic actions of leptin are mediated, in large part, by stimulation of leptin receptors (LRs) in the CNS and require activation of proopiomelanocortin (POMC) neurons and MC4R. These chronic antidiabetic effects of the CNS leptin-melanocortin system appear to be independent of autonomic nervous system and pituitary-thyroid-adrenal (PTA) axis mechanisms.SummaryThe powerful antidiabetic actions of the CNS leptin-melanocortin system are capable of normalizing plasma glucose even in the absence of insulin and involve interactions of multiple neuronal populations and intracellular signaling pathways. Although the links between the CNS leptin-melanocortin system and its chronic effects on peripheral tissue glucose metabolism are still uncertain, they are independent of insulin action, activation of the a...

Source: Current Diabetes Reports - May 25, 2020 Category: Endocrinology Source Type: research