Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors

Jennifer M. Wade, Punita Juneja, Adrienne W. MacKay, James Graham, Peter J Havel, Laurence H. Tecott, Evan H. Goulding

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

To investigate how serotonin and leptin interact in the regulation of energy balance and glucose homeostasis, we generated a genetic mouse model, the OB2C mouse, which lacks functional serotonin 2C receptors and the adipocyte hormone leptin. The OB2C mice exhibited a dramatic diabetes phenotype, evidenced by a synergistic increase in serum glucose levels and water intake. The severity of the animals' diabetes phenotype would not have been predicted from the phenotypic characterization of mice bearing mutations of either the leptin (OB mutant mice) or the serotonin 2C receptor gene (2C mutant mice). The synergistic impairment in glucose homeostasis developed at an age when OB2C mice did not differ in body weight from OB mice, suggesting that this impairment was not an indirect consequence of increased adiposity. We also demonstrated that the improvement in glucose tolerance in wild-type mice treated with the serotonin releaser and reuptake inhibitor fenfluramine was blunted in 2C mutant mice. These pharmacological and genetic findings provide evidence that the serotonin 2C receptor has direct effects on glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)955-961
Number of pages7
JournalEndocrinology
Volume149
Issue number3
DOIs
StatePublished - Mar 2008

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Receptor, Serotonin, 5-HT2C
Homeostasis
Glucose
Leptin
Fenfluramine
Phenotype
Genetic Models
Adiposity
Serotonin Uptake Inhibitors
Adipocytes
Drinking
Serotonin
Body Weight
Hormones
Pharmacology

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Wade, J. M., Juneja, P., MacKay, A. W., Graham, J., Havel, P. J., Tecott, L. H., & Goulding, E. H. (2008). Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors. Endocrinology, 149(3), 955-961. https://doi.org/10.1210/en.2007-0927

Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors. / Wade, Jennifer M.; Juneja, Punita; MacKay, Adrienne W.; Graham, James; Havel, Peter J; Tecott, Laurence H.; Goulding, Evan H.

In: Endocrinology, Vol. 149, No. 3, 03.2008, p. 955-961.

Research output: Contribution to journalArticle

Wade, JM, Juneja, P, MacKay, AW, Graham, J, Havel, PJ, Tecott, LH & Goulding, EH 2008, 'Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors', Endocrinology, vol. 149, no. 3, pp. 955-961. https://doi.org/10.1210/en.2007-0927
Wade, Jennifer M. ; Juneja, Punita ; MacKay, Adrienne W. ; Graham, James ; Havel, Peter J ; Tecott, Laurence H. ; Goulding, Evan H. / Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors. In: Endocrinology. 2008 ; Vol. 149, No. 3. pp. 955-961.
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