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An Old Dog Learns a New Trick: Regulation of Peripheral Glucose Homeostasis by the Serotonin (5-HT)_2C Receptor

Bristol-Myers Squibb, Metabolic Diseases Research, HPW 21-2.03, Discovery Biology, Princeton, NJ, 08543-5400

SUMMARY

New findings indicate that the serotonin subtype 2C receptor (5-HT_2CR) activation results in improved peripheral glucose control in mice. Furthermore, this effect seems to depend on the involvement of the melanocortin system. This appears to be the first demonstration of a link between 5-HT_2CR activation and glucose regulation, independent of food intake and body weight reductions. These findings may have immediate implications in humans, as there are selective 5-HT_2CR agonists currently in advanced clinical trials. There is historical utility to these observations as well, putting into perspective past findings from studies utilizing fenfluramine that hinted at links between the serotonin system and glucose control. Recent discoveries linking hypothalamic nutrientsensing systems and glucose homeostasis are considered, and these underscore the role of the serotonin system in the complicated phenomenon of peripheral glucose regulation.