Glycation and HMG-CoA Reductase Inhibitors: Implication in Diabetes and Associated Complications

Author(s): Rabia Nabi, Sahir Sultan Alvi, Mohd. Saeed, Saheem Ahmad, Mohammad Salman Khan*

Journal Name: Current Diabetes Reviews

Volume 15 , Issue 3 , 2019

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Introduction: 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.

Objective: 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.

Conclusion: 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.

Keywords: Glycation, Advanced Glycation end products (AGEs), HMG-R inhibitors, diabetic complications, Cardiovascular disease (CVD), Receptor for AGEs (RAGE).

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Year: 2019
Page: [213 - 223]
Pages: 11
DOI: 10.2174/1573399814666180924113442
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