Nabi Rabia, Alvi Sahir Sultan, Saeed Mohammad, Ahmad Saheem, Khan Mohammad Salman
Clinical Biochemistry & Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P, India.
Department of Clinical Lab. Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia.
Curr Diabetes Rev. 2019;15(3):213-223. doi: 10.2174/1573399814666180924113442.
Diabetes Mellitus (DM) acts as an absolute mediator of cardiovascular risk, prompting the prolonged occurrence, size and intricacy of atherosclerotic plaques via enhanced Advanced Glycation Endproducts (AGEs) formation. Moreover, hyperglycemia is associated with enhanced glyco-oxidized and oxidized Low-Density Lipoprotein (LDL) possessing greater atherogenicity and decreased the ability to regulate HMG-CoA reductase (HMG-R). Although aminoguanidine (AG) prevents the AGE-induced protein cross-linking due to its anti-glycation potential, it exerts several unusual pharmaco-toxicological effects thus restraining its desirable therapeutic effects. HMG-R inhibitors/ statins exhibit a variety of beneficial impacts in addition to the cholesterol-lowering effects.
Inhibition of AGEs interaction with receptor for AGEs (RAGE) and glyco-oxidized-LDL by HMG-R inhibitors could decrease LDL uptake by LDL-receptor (LDL-R), regulate cholesterol synthesis via HMG-R, decrease oxidative and inflammatory stress to improve the diabetes-associated complications.
Current article appraises the pathological AGE-RAGE concerns in diabetes and its associated complications, mainly focusing on the phenomenon of both circulatory AGEs and those accumulating in tissues in diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy, discussing the potential protective role of HMG-R inhibitors against diabetic complications.
糖尿病（DM）是心血管风险的绝对介导因素，通过增强晚期糖基化终产物（AGEs）的形成，促使动脉粥样硬化斑块长期形成、增大并变得复杂。此外，高血糖与糖氧化和氧化的低密度脂蛋白（LDL）增加有关，后者具有更大的致动脉粥样硬化性，并降低了调节3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-R）的能力。尽管氨基胍（AG）因其抗糖基化潜力可防止AGE诱导的蛋白质交联，但其会产生一些异常的药理毒理学效应，从而限制了其理想的治疗效果。HMG-R抑制剂/他汀类药物除了具有降低胆固醇的作用外，还表现出多种有益影响。
HMG-R抑制剂抑制AGEs与AGE受体（RAGE）以及糖氧化LDL的相互作用，可减少LDL受体（LDL-R）对LDL的摄取，通过HMG-R调节胆固醇合成，降低氧化应激和炎症应激，以改善糖尿病相关并发症。
本文评估了糖尿病及其相关并发症中AGE-RAGE的病理问题，主要关注循环AGEs以及在糖尿病肾病、糖尿病神经病变和糖尿病视网膜病变中在组织中积累的AGEs的现象，讨论了HMG-R抑制剂对糖尿病并发症的潜在保护作用。
