Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
Department of Internal Medicine, School of Medicine, University of Crete, Heraklion, Greece.
Diabetes Metab Res Rev. 2019 Mar;35(3):e3118. doi: 10.1002/dmrr.3118. Epub 2019 Jan 7.
Apolipoprotein CIII (ApoCIII), a small protein that resides on the surface of lipoprotein particles, is a key regulator of triglyceride metabolism. The inhibition of lipoprotein lipase (LPL), the increased assembly and secretion of very low-density lipoproteins (VLDL) and the decreased reuptake of triglyceride-rich lipoproteins (TRLs) by the liver are mechanisms associating elevated serum ApoCIII levels and hypertriglyceridemia. ApoCIII concentration is high in individuals with diabetes mellitus, indicating a possible positive correlation with impairment of glucose metabolism. The aim of this review (based on a Pubmed search until August 2018) is to present the possible mechanisms linking ApoCIII and deterioration of carbohydrate homeostasis. ApoCIII enhances pancreatic β-cells apoptosis via an increase of the cytoplasmic Ca levels in the insulin-producing cells. In addition, overexpression of ApoCIII enhances non-alcoholic fatty liver disease and exacerbates inflammatory pathways in skeletal muscles, affecting insulin signalling and thereby inducing insulin resistance. Moreover, recent studies reveal a possible mechanism of body weight increase and glucose production through a potential ApoCIII-induced LPL inhibition in the hypothalamus. Also, the presence of ApoCIII on the surface of high-density lipoprotein particles is associated with impairment of their antiglycemic and atheroprotective properties. Modulating ApoCIII may be a potent therapeutic approach to manage hypertriglyceridemia and improve carbohydrate metabolism.
载脂蛋白 CIII（ApoCIII）是一种位于脂蛋白颗粒表面的小蛋白，是甘油三酯代谢的关键调节因子。脂蛋白脂肪酶（LPL）抑制、极低密度脂蛋白（VLDL）组装和分泌增加以及富含甘油三酯的脂蛋白（TRLs）在肝脏中的再摄取减少，这些机制与血清 ApoCIII 水平升高和高甘油三酯血症有关。糖尿病患者的 ApoCIII 浓度较高，表明与葡萄糖代谢受损可能存在正相关。本综述（基于截至 2018 年 8 月的 Pubmed 检索）的目的是介绍可能将 ApoCIII 与碳水化合物稳态恶化联系起来的机制。ApoCIII 通过增加产生胰岛素的细胞中的细胞质 Ca 水平来增强胰腺β细胞凋亡。此外，ApoCIII 的过表达会加剧非酒精性脂肪性肝病和骨骼肌中的炎症途径，影响胰岛素信号传导，从而导致胰岛素抵抗。此外，最近的研究揭示了一种可能的机制，即通过潜在的 ApoCIII 在下丘脑抑制脂蛋白脂肪酶，导致体重增加和葡萄糖生成。此外，高密度脂蛋白颗粒表面的 ApoCIII 存在与损害其抗糖尿病和抗动脉粥样硬化特性有关。调节 ApoCIII 可能是治疗高甘油三酯血症和改善碳水化合物代谢的有效方法。
