Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital of Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany. norbert.stefan@ med.uni-tuebingen.de
Nat Rev Endocrinol. 2013 Mar;9(3):144-52. doi: 10.1038/nrendo.2012.258. Epub 2013 Jan 22.
The liver is known to be involved in the natural history of the ongoing epidemics of type 2 diabetes mellitus and cardiovascular disease. In particular, the liver has a role in increased glucose production and dysregulated lipoprotein metabolism, conditions that are often found in patients with nonalcoholic fatty liver disease. Additionally, several proteins that are exclusively or predominantly secreted from the liver are now known to directly affect glucose and lipid metabolism. In analogy to the functional proteins released from adipose tissue and skeletal muscle-adipokines and myokines-these liver-derived proteins are known as hepatokines. The first hepatokine that has been proven to have a major pathogenetic role in metabolic diseases is α2-HS-glycoprotein (fetuin-A). Production of this glycoprotein is increased in steatotic and inflamed liver, but not in expanded and dysregulated adipose tissue. Thus, research into this molecule and other hepatokines is expected to aid in differentiating between the contribution of liver and those of skeletal muscle and adipose tissue, to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease.
肝脏被认为与 2 型糖尿病和心血管疾病的持续流行的自然史有关。特别是，肝脏在增加葡萄糖生成和脂蛋白代谢失调方面发挥作用，这些情况在非酒精性脂肪性肝病患者中经常出现。此外，现在已知几种专门或主要从肝脏分泌的蛋白质可直接影响葡萄糖和脂质代谢。类似于从脂肪组织和骨骼肌释放的功能性蛋白质（脂肪因子和肌因子），这些肝脏来源的蛋白质被称为肝因子。已被证明在代谢性疾病中具有主要发病作用的第一种肝因子是α2-HS-糖蛋白（胎球蛋白-A）。这种糖蛋白的产生在脂肪变性和炎症的肝脏中增加，但在扩张和失调的脂肪组织中没有增加。因此，对该分子和其他肝因子的研究有望有助于区分肝脏与骨骼肌和脂肪组织对 2 型糖尿病和心血管疾病发病机制的贡献。
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