The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes.

The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes.
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DOI:
10.1038/nature13478
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发表时间:
2014-06-05
期刊:
影响因子:
64.8
通讯作者:
Shulman, Gerald I.
Shulman, Gerald I.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Perry, Rachel J.;Samuel, Varman T.;Petersen, Kitt F.;Shulman, Gerald I.

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非酒精性脂肪肝及其下游后遗症、肝脏胰岛素抵抗和2型糖尿病是迅速增长的流行病,导致发病率和死亡率增加,医疗保健费用飙升。制定干预措施需要全面了解过量肝脏脂质发展和导致肝脏胰岛素抵抗和2型糖尿病的机制。提出的机制涉及各种脂质种类、炎症信号传导和其他细胞修饰。在小鼠和人类中的研究已经阐明了蛋白激酶Cε的肝二酰甘油激活在触发肝胰岛素抵抗中的关键作用。基于这种机制的治疗方法可以减轻非酒精性脂肪肝和2型糖尿病的相关流行。
Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.
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