Effect Of Chronic Olanzapine Treatment On The Expression Of Insulin Resistance-related Proteins In Balb/c Mice

[OBJECTIVE] Abnormal glucose and lipid metabolism in schizophrenia with antipsychotic treatment have become more apparent and impact seriously on the efficacy of mental illness. It has become a thorny issue in the clinical treatment of antipsychotic. Atypical antipsychotics has been the first line drugs for the treatment of psychosis and mood disorders. Despite the beneficial effects in patient, atypical antipsychotics use is accompanied by some adverse metabolic effects such dyslipidemia, glucose intolerance and insulin resistance. The molecular mechanisms underlying these adverse effects are not fully understood and remain to be elucidated. Here we investigated the effect of chronic treatment of olanzapine on the expression of lipid metabolism-related proteins and insulin resistance in mice.[METHODS] 30 eight-week-old female Balb/c mice were randomly divied into 2 groups,which 10 in control group and 20 in olanzapine group. Olanzapine group were treated intraperitoneally with olanzapine(10mg/kg/day) for 8 weeks. Body weight, fast glucose and insulin levels were measured every week. After the treatment, the olanzapine group mice were equally assigned in two groups: insulin-resistant mice(IR mice) and insulin-sensitive mice(IS mice) according to their homeostasis model assessment-insulin resistance(HOMA-IR) index. Oral glucose tolerance test(OGTT) was measured at baseline and after the treatment. Protein levels were determined using western blot in adipose tissue and plasma.[RESULTS](1) The results showed that levels of serum insulin and glucose were significantly increased in IR mice. Moreover, olanzapine treatment significantly increased values of area under the curve for glucose(AUCglucose) in OGTT and HOMA-IR index in IR mice, indicating the deteriorating effect on glucose tolerance and insulin signaling in mice. However, no significant increases in weight were observed at week 8.(2) The Western blot analysis revealed that expressions of lipid metabolism related proteins, such as FAT, PTP-1B, GGPPS, GRK2 and ATGL were significantly elevated in adipose tissue in IR mice. On the other hand, expressions of proteins such as FGF21 and PGC-1α were down-regulated in adipose tissue in IR mice. The protein expressions in plasma showed the same tendency as the results in adipose tissue.[CONCLUSION] In this study, expressions of proteins such as FAT, PTP-1B, GRK2 and ATGL have significant differences in adipose tissue and plasma with IR mice and IS mice by chronic olanzapine treatment. The results may contribute to the understanding of the relationship between the insulin resistance and the chronic treatment of olanzapine.