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Erschienen in: Current Diabetes Reports 7/2020

01.07.2020 | Obesity (KM Gadde and P Singh, Section Editors)

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

verfasst von: Alexandre A. da Silva, Jussara M. do Carmo, John E. Hall

Erschienen in: Current Diabetes Reports | Ausgabe 7/2020

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Abstract

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.
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Zurück zum Zitat •• da Silva AA, Hall JE, Moak SP, Browning J, Houghton HJ, Micheloni GC, et al. Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin. Am J Physiol Endocrinol Metab. 2017;312(5):E420–E8. https://doi.org/10.1152/ajpendo.00301.2016. This study demonstrates that leptin's powerful chronic CNS-mediated antidiabetic actions are independent of leptin's ability to modulate autonomic nervous system activity and suggest that a circulating factor may contribute importantly to the effects of leptin on glucose homeostasis in the absence of insulin actions. •• da Silva AA, Hall JE, Moak SP, Browning J, Houghton HJ, Micheloni GC, et al. Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin. Am J Physiol Endocrinol Metab. 2017;312(5):E420–E8. https://​doi.​org/​10.​1152/​ajpendo.​00301.​2016. This study demonstrates that leptin's powerful chronic CNS-mediated antidiabetic actions are independent of leptin's ability to modulate autonomic nervous system activity and suggest that a circulating factor may contribute importantly to the effects of leptin on glucose homeostasis in the absence of insulin actions.
Metadaten
Titel
CNS Regulation of Glucose Homeostasis: Role of the Leptin-Melanocortin System
verfasst von
Alexandre A. da Silva
Jussara M. do Carmo
John E. Hall
Publikationsdatum
01.07.2020
Verlag
Springer US
Erschienen in
Current Diabetes Reports / Ausgabe 7/2020
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-020-01311-1

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