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Emerging Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease, Insulin Resistance, and Type 2 Diabetes.
Annual Review of Pharmacology and Toxicology ( IF 12.5 ) Pub Date : 2019-01-06 , DOI: 10.1146/annurev-pharmtox-010716-104727
Leigh Goedeke 1 , Rachel J Perry 1, 2 , Gerald I Shulman 1, 2, 3
Affiliation  

Type 2 diabetes (T2D) is characterized by persistent hyperglycemia despite hyperinsulinemia, affects more than 400 million people worldwide, and is a major cause of morbidity and mortality. Insulin resistance, of which ectopic lipid accumulation in the liver [nonalcoholic fatty liver disease (NAFLD)] and skeletal muscle is the root cause, plays a major role in the development of T2D. Although lifestyle interventions and weight loss are highly effective at reversing NAFLD and T2D, weight loss is difficult to sustain, and newer approaches aimed at treating the root cause of T2D are urgently needed. In this review, we highlight emerging pharmacological strategies aimed at improving insulin sensitivity and T2D by altering hepatic energy balance or inhibiting key enzymes involved in hepatic lipid synthesis. We also summarize recent research suggesting that liver-targeted mitochondrial uncoupling may be an attractive therapeutic approach to treat NAFLD, nonalcoholic steatohepatitis, and T2D.

中文翻译:

治疗非酒精性脂肪肝、胰岛素抵抗和 2 型糖尿病的新兴药理学靶点。

2 型糖尿病 (T2D) 的特点是尽管存在高胰岛素血症,但仍以持续高血糖为特征,影响全球超过 4 亿人,并且是发病率和死亡率的主要原因。胰岛素抵抗在 T2D 的发展中起主要作用,其中肝脏 [非酒精性脂肪性肝病 (NAFLD)] 和骨骼肌中的异位脂质积累是根本原因。尽管生活方式干预和减肥在逆转 NAFLD 和 T2D 方面非常有效,但减肥难以持续,迫切需要旨在治疗 T2D 根本原因的新方法。在这篇综述中,我们重点介绍了旨在通过改变肝脏能量平衡或抑制参与肝脏脂质合成的关键酶来改善胰岛素敏感性和 T2D 的新兴药理学策略。
更新日期:2016-01-20
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