Insulin Resistance–Related Proteins Are Overexpressed in Patients and Rats Treated With Olanzapine and Are Reverted by Pueraria in the Rat Model. Issue 3 (May 2019)

• Record Type: Journal Article
• Authors: Yang, Ni; Li, Shihong; Liu, Shouqing; Lv, Yifan; Yu, Liangyu; Deng, Yahui; Li, Huqun; Fang, Maosheng; Huo, Yunxiang; Li, Weiyong; Peng, Shiyong
• Is Part Of: Journal of clinical psychopharmacology. Volume 39:Issue 3(2019)
• Publication Date: 2019-05
• Subjects: insulin resistance -- insulin resistance-related proteins (IRRPs) -- olanzapine -- Pueraria -- schizophrenia; Psychopharmacology -- Periodicals; Psychopharmacology -- Periodicals; Psychopharmacologie -- Périodiques; Psychopharmacology; Periodicals; 615.78
• DOI: 10.1097/JCP.0000000000001028
• Languages: English
• ISSNs: 0271-0749

Abstract

Abstract: Background: Olanzapine, a commonly used second-generation antipsychotic, causes severe metabolic adverse effects, such as elevated blood glucose and insulin resistance (IR). Previous studies have proposed that overexpression of CD36, GGPPS, PTP-1B, GRK2, and adipose triglyceride lipase may contribute to the development of metabolic syndrome, and Pueraria could eliminate the metabolic adverse effects. The study aimed to investigate the association between olanzapine-associated IR and IR-related proteins (IRRPs) and determine the role of Pueraria in protection against the metabolic adverse effects of olanzapine. Methods: The expression levels of IRRPs were examined in schizophrenia patients and rat models with long-term olanzapine treatment. The efficacy of Pueraria on anti-IR by reducing the expression of IRRPs was comprehensively evaluated. Results: Our study demonstrated that in schizophrenia patients chronically treated with olanzapine, the expression levels of IRRPs in patients with a high IR index significantly increased, and these phenomena were further confirmed in a rat model. The expression levels of IRRPs were reduced significantly in Pueraria -treated IR rat models. The body weight, blood glucose, and IR index were restored to levels similar to those of normal controls. Conclusions: The IRRPs are closely related to IR induced by olanzapine, and Pueraria could interfere with olanzapine-associated IR and revert overexpressed IRRPs. These findings suggest that IRRPs are key players in olanzapine-associated IR and that Pueraria has potential as a clinical drug to prevent the metabolic adverse effects of olanzapine, further improving compliance of schizophrenia patients. Abstract : Supplemental digital content is available in the text.