Poh Z X, Goh K P
Medical Officer, Department of General Medicine, Alexandra Hospital, Singapore.
Endocr Metab Immune Disord Drug Targets. 2009 Dec;9(4):392-8. doi: 10.2174/187153009789839147.
Type 2 Diabetes Mellitus (T2DM) which is characterised by insulin resistance, is closely linked to the triad of glucolipotoxicity, inflammation and oxidative stress. Increased adiposity, leading to increased free fatty acids (FFAs), contributes to insulin resistance by disrupting the signal transduction pathway of insulin mediated glucose disposal, and causes impaired insulin secretion. Hyperglycaemia and dyslipidaemia driven oxidative stress resulting from enhanced free-radical formation and/or defects in antioxidant defence is implicated in the pathogenesis of diabetic neuropathy (DN). This and other inflammatory pathways account for a complex network of interacting metabolic factors responsible for causing diabetes and her complications. There is growing evidence that Alpha Lipoic Acid (ALA) has beneficial effects on the treatment of T2DM and some of its complications. It represents an attractive pharmacological target in the treatment of T2DM by modulating the signal transduction pathways in insulin resistance and antagonizing the oxidative and inflammatory stresses, which are major players in the pathogenesis of this disorder. A potent anti-oxidant and free radical scavenger, ALA also targets cellular signal transduction pathways which increases glucose uptake and utilization, thus providing specific targeted therapy in the treatment of insulin resistance and diabetic neuropathy. Apart from the rare risk of Insulin Autoimmune Syndrome (IAS), ALA has shown to be relatively safe, even in patients with renal and liver failure. This review focuses and summarises the molecular mechanisms of T2DM, and underlines the therapeutic value of ALA in this globally significant disease.
2型糖尿病(T2DM)以胰岛素抵抗为特征,与糖脂毒性、炎症和氧化应激三联征密切相关。肥胖增加导致游离脂肪酸(FFA)增多,通过破坏胰岛素介导的葡萄糖处置信号转导途径导致胰岛素抵抗,并引起胰岛素分泌受损。由自由基形成增加和/或抗氧化防御缺陷导致的高血糖和血脂异常驱动的氧化应激与糖尿病神经病变(DN)的发病机制有关。这一炎症途径和其他炎症途径构成了一个负责导致糖尿病及其并发症的相互作用的代谢因子复杂网络。越来越多的证据表明,α硫辛酸(ALA)对T2DM及其一些并发症的治疗具有有益作用。通过调节胰岛素抵抗中的信号转导途径并对抗氧化应激和炎症应激(这是该疾病发病机制中的主要因素),它在T2DM治疗中代表了一个有吸引力的药理学靶点。ALA作为一种有效的抗氧化剂和自由基清除剂,还靶向细胞信号转导途径,增加葡萄糖摄取和利用,从而在胰岛素抵抗和糖尿病神经病变的治疗中提供特异性靶向治疗。除了罕见的胰岛素自身免疫综合征(IAS)风险外,ALA已被证明相对安全,即使在肾衰竭和肝功能衰竭患者中也是如此。本综述聚焦并总结了T2DM的分子机制,并强调了ALA在这种全球重大疾病中的治疗价值。