@article{4c97486923574f4d882f17c9a4e64518,
title = "Serotonin 2C Receptor Agonists Improve Type 2 Diabetes via Melanocortin-4 Receptor Signaling Pathways",
abstract = "The burden of type 2 diabetes and its associated premature morbidity and mortality is rapidly growing, and the need for novel efficacious treatments is pressing. We report here that serotonin 2C receptor (5-HT2CR) agonists, typically investigated for their anorectic properties, significantly improve glucose tolerance and reduce plasma insulin in murine models of obesity and type 2 diabetes. Importantly, 5-HT2CR agonist-induced improvements in glucose homeostasis occurred at concentrations of agonist that had no effect on ingestive behavior, energy expenditure, locomotor activity, body weight, or fat mass. We determined that this primary effect on glucose homeostasis requires downstream activation of melanocortin-4 receptors (MC4Rs), but not MC3Rs. These findings suggest that pharmacological targeting of 5-HT2CRs may enhance glucose tolerance independently of alterations in body weight and that this may prove an effective and mechanistically novel strategy in the treatment of type 2 diabetes.",
keywords = "HUMDISEASE, MOLNEURO",
author = "Ligang Zhou and Sutton, {Gregory M.} and Rochford, {Justin J.} and Semple, {Robert K.} and Lam, {Daniel D.} and Laura J Oksanen and Thornton-Jones, {Zoe D.} and Clifton, {Peter G.} and Yueh, {Chen Yu} and Evans, {Mark L.} and Rory J McCrimmon and Elmquist, {Joel K.} and Butler, {Andrew A.} and Heisler, {Lora K.}",
note = "Funding Information: The authors were supported by the following: J.J.R., British Heart Foundation; D.D.L., the Gates Cambridge Trust; L.J.O., NIDDK R3728082 (through J.S. Flier), the Jalmari and Rauha Ahokas Foundation, and the Finnish Foundation for Cardiovascular Research; P.G.C., BBSRC C505291; J.K.E., NIMH R01 MH61583, NIDDK R01 53301, NIDDK P01 DK56116, and a Smith Family Pinnacle Award from the American Diabetes Association; A.A.B., NIDDK R21 DK068330 and the American Diabetes Association; and L.K.H., NIDDK R01 DK065171, the American Diabetes Association, the Wellcome Trust, and the Boston Obesity Nutrition Research Center. A.A.B. is a shareholder of Orexigen Therapeutics, Inc., and a consultant for Ipsen, Inc., companies that may have a commercial interest in the results of this research. ",
year = "2007",
month = nov,
day = "7",
doi = "10.1016/j.cmet.2007.10.008",
language = "English (US)",
volume = "6",
pages = "398--405",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}