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

Purpose of Review In 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 Findings Leptin...

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Bibliographic Details
Published in:Current diabetes reports 2020-07, Vol.20 (7), p.29-29, Article 29
Main Authors: da Silva, Alexandre A., do Carmo, Jussara M., Hall, John E.
Format: Article
Language:English
Subjects:
Animals
Diabetes
Glucose
Homeostasis
Humans
Insulin
Insulin resistance
Leptin
Medicine
Medicine & Public Health
Melanocortins
Metabolism
Nervous system
Obesity (KM Gadde and P Singh
Receptors, Leptin
Section Editors
Topical Collection on Obesity
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Summary:Purpose of Review In 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 Findings Leptin 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. Summary The 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 autonomic nervous system, or the PTA axis. Unraveling the pathways that contribute to the powerful antidiabetic effects of the CNS leptin-melanocortin system may provide novel therapeutic approaches for diabetes mellitus.
ISSN:1534-4827
1539-0829
DOI:10.1007/s11892-020-01311-1