Exploring the glycation association with dyslipidaemia: Novel approach for diabetic nephropathy

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Ashwini D. Jagdale , Mukul M. Angal , Rahul S. Patil , Rashmi S. Tupe
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Abstract

The transcription factor known as sterol regulatory element-binding protein (SREBP) and the glycation pathways, specifically the formation of Advanced Glycation End Products (AGEs), have a significant and deleterious impact on the kidney. They alter renal lipid metabolism and promote glomerulosclerosis, mesangial cell expansion, tubulointerstitial fibrosis, and inflammation, leading to diabetic nephropathy (DN) progression. Although several pieces of scientific evidence are reported for potential causes of glycation and lipotoxicity in DN, the underlying mechanism of renal lipid accumulation still needs to be fully understood. We provide a rationalized view on how AGEs exert multiple effects that cause SREBP activation and inflammation, contributing to DN through Receptor for AGEs (RAGE) signaling, AGE-R1-dependent downregulation of Sirtuin 1 (SIRT-1), and increased SREBP Cleavage Activating Protein (SCAP) glycosylation. This review emphasizes the association between glycation and the SREBP pathway and how it affects the onset of DN associated with obesity. Finally, we discuss the correlation of glycation and the SREBP pathway with insulin resistance (IR), oxidative stress, endoplasmic reticulum stress, inflammation, and existing and emerging therapeutic approaches toward better controlling obesity-related DN.

Abstract Image

探索糖化与血脂异常的关联:治疗糖尿病肾病的新方法。
转录因子固醇调节元件结合蛋白(SREBP)和糖化途径,特别是高级糖化终产物(AGEs)的形成,对肾脏有重大的有害影响。它们会改变肾脏脂质代谢,促进肾小球硬化、肾间质细胞扩张、肾小管间质纤维化和炎症,从而导致糖尿病肾病(DN)恶化。尽管有多种科学证据表明 DN 中糖化和脂毒性的潜在原因,但肾脏脂质蓄积的内在机制仍有待全面了解。我们对 AGEs 如何通过 AGEs 受体(RAGE)信号传导、AGE-R1 依赖性下调 Sirtuin 1(SIRT-1)和增加 SREBP 裂解激活蛋白(SCAP)糖基化等多重作用引起 SREBP 激活和炎症,从而导致 DN 的发生提供了合理的观点。本综述强调了糖化与 SREBP 通路之间的关联,以及糖化如何影响与肥胖相关的 DN 的发生。最后,我们将讨论糖化和 SREBP 通路与胰岛素抵抗 (IR)、氧化应激、内质网应激、炎症的相关性,以及现有和新兴的治疗方法,以更好地控制与肥胖相关的 DN。
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来源期刊
Biochemical pharmacology
Biochemical pharmacology 医学-药学
CiteScore
10.30
自引率
1.70%
发文量
420
审稿时长
17 days
期刊介绍: Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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