This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gilles, M. Articles by Deuschle, M. Search for Related Content PubMed PubMed Citation Articles by Gilles, M. Articles by Deuschle, M. Related Collections Diabetes

Antagonism of the Serotonin (5-HT)-2 Receptor and Insulin Sensitivity: Implications for Atypical Antipsychotics

From the Central Institute of Mental Health, Mannheim, Germany (M.G., A.W., D.K., A.N., M.D.); Department of Endocrinology and Metabolism, Otto-von-Guericke-University, Magdeburg, Germany (H.L.).

Address correspondence and reprint requests to Maria Gilles, MD, Central Institute of Mental Health, J5, 68159 Mannheim, Germany. E-mail: gilles{at}as200.zi-mannheim.de

Objective: Both conventional and second-generation antipsychotics have been associated with an increased risk for impaired glucose tolerance and diabetes mellitus. Though this has been largely attributed to weight gain, there may also be a direct, receptor-mediated effect of antipsychotics on glucose tolerance. We tested the hypothesis that antagonism of the serotonin (5-HT)-2 receptor impairs insulin sensitivity.

Methods: Ten healthy male volunteers were included in a double-blind, placebo-controlled crossover study of a single dose of 40 mg of the 5-HT₂ antagonist ketanserin versus placebo. Insulin sensitivity was measured by means of the euglycemic-hyperinsulinemic clamp technique. Subjects were treated with the -1 adrenergic antagonist phenoxybenzamine in both parts of the study to control for ketanserin’s effects at the level of this receptor.

Results: Compared with the placebo condition, subjects showed a significantly decreased insulin sensitivity after ketanserin (placebo: 9.4 ± 3.6 mg/kg/min; ketanserin: 7.7 ± 2.1 mg/kg/min; p = .047).

Conclusion: The selective 5-HT₂ antagonist ketanserin impaired insulin sensitivity. This effect was possibly mediated by suppression of 5-HT_2A receptor mediated glucose uptake in skeletal muscle.

Key Words: 5-HT₂ antagonism • impaired insulin sensitivity • euglycemic-hyperinsulinemic clamp technique

Abbreviations: 5-HT = 5-hydroxytryptamine (serotonin); BMI = body mass index; FPG = fasting plasma glucose; IS = insulin sensitivity; BP = blood pressure.