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雌性Balb/C小鼠首次发作的精神分裂症、代谢综合征与胰岛素抵抗相关蛋白之间的关联

Association Between First Episode Schizophrenia, Metabolic Syndrome and Insulin Resistance-Related Proteins in Female Balb/C Mice.

作者信息

Sattar Haseeb, Li Huqun, Han Yong, Zhou Hong, Darbalaei Sanaz, Li Weiyong

机构信息

Department of Clinical Pharmacy, Wuhan Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Galen Med J. 2018 Apr 1;7:e692. doi: 10.22086/gmj.v0i0.692. eCollection 2018.

Abstract

BACKGROUND

Metabolic syndrome is a group of different disorders mainly includes, insulin resistance, obesity, cerebrovascular disorders, dyslipidemia, which leads to increase mortality. Patients suffering from related psychotic disorders such as schizophrenia are at the higher risk of developing metabolic syndrome. The aim of this study was to evaluate the association between the first episode of schizophrenia, metabolic syndrome and insulin resistance-related proteins in blood and adipose tissue of mice.

MATERIALS AND METHODS

Twelve, female Balb/c mice were randomly divided into two groups; one group was injected intraperitoneal MK-801(0.6mg/kg/d) to induce schizophrenia, and other group received the 0.9% normal saline for two weeks. Body weight, fasting blood glucose (FBG), oral glucose tolerance (OGT), and Homeostatic model assessment (HOMA), were observed. Blood and adipose tissue were collected and Western blotting was done to evaluate the insulin resistance related proteins (GGPPS, FAT, PTP-1B, GRK2, ATGL, FGF21, and PGC-1α) by using GAPDH as an internal standard.

RESULTS

There was a significant increase in mean body weight in schizophrenic group (21.76 vs 22.81, P=004). On day 14, the FBG, insulin concentrations and Homeostatic model assessment and insulin resistance (HOME-IR) were high in schizhphrenic group vs control group, e.g. 5.3±0.6 vs 3.47±0.2 (P=0.0001), 28.9±2.2 vs 23.3±0.6 (P<0.005) and 9.2±1.3 vs 3.9±0.2 (P=0.0001) . Impaired glucose tolerance deranged from 4.8mmol/L to 6.4mmol/L. Western blotting showed a marked increase in the expression of GGPPS, FAT, ATGL, and FGF21 proteins in monocytes and PTP-1B, GRK2, and PGC-1α ratios in adipose tissues.

CONCLUSION

There was a positive relation between schizophrenia and metabolic syndrome e.g. insulin resistance and obesity. Certain proteins in adipocytes and blood were responsible for causing insulin resistance.

摘要

背景

代谢综合征是一组不同的病症,主要包括胰岛素抵抗、肥胖、脑血管疾病、血脂异常,这些会导致死亡率增加。患有精神分裂症等相关精神障碍的患者患代谢综合征的风险更高。本研究的目的是评估小鼠首次发作精神分裂症、代谢综合征与血液和脂肪组织中胰岛素抵抗相关蛋白之间的关联。

材料与方法

将12只雌性Balb/c小鼠随机分为两组;一组腹腔注射MK-801(0.6mg/kg/d)以诱导精神分裂症,另一组接受0.9%生理盐水注射两周。观察体重、空腹血糖(FBG)、口服葡萄糖耐量(OGT)和稳态模型评估(HOMA)。采集血液和脂肪组织,进行蛋白质免疫印迹分析,以甘油醛-3-磷酸脱氢酶(GAPDH)作为内参,评估胰岛素抵抗相关蛋白(香叶基香叶基焦磷酸合酶(GGPPS)、脂肪酸转运蛋白(FAT)、蛋白酪氨酸磷酸酶1B(PTP-1B)、G蛋白偶联受体激酶2(GRK2)、脂肪甘油三酯脂肪酶(ATGL)、成纤维细胞生长因子21(FGF21)和过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α))。

结果

精神分裂症组的平均体重显著增加(21.76对22.81,P = 0.04)。在第14天,精神分裂症组的空腹血糖、胰岛素浓度、稳态模型评估和胰岛素抵抗(HOMA-IR)均高于对照组,例如5.3±0.6对3.47±0.2(P = 0.0001)、28.9±2.2对23.3±0.6(P < 0.005)和9.2±1.3对3.9±0.2(P = 0.0001)。葡萄糖耐量受损,从4.8mmol/L变化至6.4mmol/L。蛋白质免疫印迹分析显示,单核细胞中GGPPS、FAT、ATGL和FGF21蛋白的表达显著增加,脂肪组织中PTP-1B、GRK2和PGC-1α的比例增加。

结论

精神分裂症与代谢综合征(如胰岛素抵抗和肥胖)之间存在正相关关系。脂肪细胞和血液中的某些蛋白质导致了胰岛素抵抗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304d/8343899/11d86c51f922/gmj-7-e692-g001.jpg

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