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KMID : 0605620120190040187
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Journal of Korean Society of Biological Psychiatry
2012 Volume.19 No. 4 p.187 ~ p.192
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The Effect of Clozapine on Central Insulin Response in Rats
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Kim Se-Hyun
Yu Hyun-Sook
Park So-Young
Kim Min-Kyung
Park Hong-Geun
Kim Yong-Sik
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Abstract
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Objectives: Although antipsychotic drug clozapine has superior efficacy, this is hampered by metabolic side effects such as weight gain and diabetes. Recent studies demonstrate that clozapine induces insulin resistance. However, the identity and location of insulin resistance induced by clozapine has not been clarified. In this study, the effect of clozapine on central insulin response was investigated in rats.
Methods: Male Sprague-Dawley rats received intraperitoneal injection of clozapine or vehicle, which was followed by intracerebroventricular injection of insulin or its vehicle. The effects of clozapine on insulin-induced changes in blood glucose level and Akt phosphorylation in hypothalamus were investigated.
Results: Intraperitoneal injection of clozapine (20 mg/kg) increased blood glucose in rats. Intracerebroventricular injection of insulin reduced blood glucose in rats, which was blunted by pretreatment of clozapine. Accompanied with the antagonistic effect of clozapine to central insulin action in terms of blood glucose, clozapine inhibited the insulin-induced phosphorylation of Akt at Ser473 in rat hypothalamus.
Conclusion: Administration of clozapine inhibited the central insulin-induced changes in blood glucose and Akt phosphorylation in rat hypothalamus. These findings suggest that hypothalamus could be the site of action for the clozapine-induced insulin resistance.
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KEYWORD
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Atypical antipsychotics, Insulin resistance, Blood glucose, Hypothalamus, Akt
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