Am J Physiol Endocrinol Metab:糖尿病猕猴研究获进展

2018-05-05 佚名 昆明动物所

糖尿病(Diabetes Mellitus, DM)是一种严重危害人类健康的代谢性疾病,是目前全世界发病率和死亡率最高的5种疾病之一。近年来,随着人们生活水平的提高以及人口老龄化问题逐渐加重,糖尿病发病率逐年上升。据世界卫生组织(WHO)报道,截至2015年,全球有4.15亿糖尿病患者,而中国是世界第一糖尿病大国。

糖尿病(Diabetes Mellitus, DM)是一种严重危害人类健康的代谢性疾病,是目前全世界发病率和死亡率最高的5种疾病之一。近年来,随着人们生活水平的提高以及人口老龄化问题逐渐加重,糖尿病发病率逐年上升。据世界卫生组织(WHO)报道,截至2015年,全球有4.15亿糖尿病患者,而中国是世界第一糖尿病大国。

大量流行病学数据显示,肥胖是2型糖尿病发病的独立危险因素,但肥胖如何导致糖尿病还有很多未知。目前关于肥胖与2型糖尿病的研究,绝大部分是使用小鼠和大鼠等啮齿类动物,通过急性高热量食物诱导,或者化学药物损伤胰岛β细胞构建的。然而,这些非自然方式构建的啮齿类动物模型常常不能很好地模拟人类2型糖尿病。与此相反,非人灵长类动物如猕猴(Macaca mulatta)与人类的遗传背景和生理结构更为接近,其自发性糖尿病病程和病症与人类糖尿病更为相似,是研究人类2型糖尿病的极佳动物模型。

中国科学院昆明动物研究所梁斌团队和中国科学院生物物理研究所刘平生团队合作,历经四年,对昆明动物所饲养的2000多只猕猴进行了大规模筛选,从中成功筛选出一批自发性肥胖和自发性糖尿病猕猴;进一步观察发现,这些猕猴的生理生化指标和人类肥胖和糖尿病非常接近。随后,他们和中科院上海药物研究所周虎团队合作,对自发性肥胖和糖尿病猕猴肝脏进行蛋白质组学研究。肝脏蛋白质组学数据分析和功能实验表明,自发性肥胖猕猴肝脏出现脂肪肝,脂肪酸氧化途径和脂肪合成途径明显上调。该表型和高热量诱导的小鼠模型差别很大,但和人类脂肪肝的表型十分类似。自发性糖尿病猕猴早期出现肥胖和高血脂,而晚期体重和血脂指标下降,出现明显的肝脏损伤;肝脏蛋白质组学显示,氧化磷酸化途径和支链氨基酸降解途径明显上调,肝脏损伤可能是肝脏中过多的ROS通过诱导线粒体释放细胞色素c,并激活胞质中Caspase3所致。该研究首次揭示在自然状况下,由肥胖转为糖尿病过程中,肝脏能量代谢出现从脂肪酸氧化到支链氨基酸降解的转变,为肥胖导致糖尿病的发病机制提供了新的思路。

该研究成果目前在线发表于美国生理学会期刊American Journal of Physiology- Endocrinology and Metabolism。该项工作得到国家自然科学基金、中科院先导专项、云南省自然科学基金、云南省高端科技人才项目等的资助。

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    2018-06-24 guojianrong
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    2018-07-09 一闲
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    2018-05-05 131****1460

    学习了受益匪浅

    0

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    2018-05-05 三生有幸9135

    学习一下谢谢分享

    0

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