[翻译]胰岛素抵抗与慢性肝病

Insulin resistance: A metabolic pathway to chronic liver disease.
Bugianesi E, McCullough AJ, Marchesini G.
Gastroenterology Department, University of Turin, Turin, Italy.
Hepatology. 2005 Nov;42(5):987-1000.
Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic liver disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic liver disease is associated with multiple features of the metabolic syndrome, and the risk of progressive liver disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.

胰岛素抵抗是非酒精性脂肪肝的病理生理特点，是西方国家中慢性肝病的最常见原因之一。我们综述了胰岛素抵抗的定义、定量评价胰岛素作用的方法、胰岛素抵抗的病理生理以及胰岛素抵抗在慢性肝病发病机制中的作用。异常的脂肪代谢导致更多的游离脂肪酸从脂肪组织转移至非脂肪组织，这会引起肝脏甘油三酯的积聚，削弱肌肉和肝组织的糖代谢和胰岛素的敏感性。脂肪细胞分泌或表达的几种因子参与了前炎症阶段的始动环节，而前炎症阶段既可能仅限于肝脏，也可能是波及全身的。胰岛素抵抗为代谢综合征的常见特征，它是一系统性疾病，可以影响到神经系统、肌肉组织、胰腺、肾脏、心脏、免疫系统及肝脏。对于患者个体，基因与环境间复杂的相互作用增强了胰岛素抵抗和非酒精性脂肪肝表型的表达。进一步的肝纤维化与代谢综合征的诸多方面有关，而对于患代谢性疾病的个体，肝病进一步发展（指肝纤维化、肝硬化）的危险不容被低估。最后，对胰岛素增敏剂的作用能力以及治疗非酒精性脂肪肝的药物（二甲双胍：减少肝脏胰岛素抵抗；噻唑烷二酮类：减少外周组织胰岛素抵抗）进行了讨论。