Mitochondrial dysfunction in diabetic tubulopathy

Yao, Lan; Liang, Xianhui; Qiao, Ye; Chen, Bohan; Wang, Pei; Liu, Zhangsuo

doi:10.1016/j.metabol.2022.155195

Cited by 74 publications

(38 citation statements)

References 124 publications

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“…High glucose-induced oxidative stress and mitochondrial dysfunction interact to promote the progression of DM and its complications ( 63 ). One article focused on the relationship between diabetic renal tubular injury and mitochondrial dysfunction, contributing to increased ROS production and metabolic abnormalities such as abnormal mitochondrial autophagy, and the article suggested that mitochondrial dysfunction may contribute to early diabetic tubulopathy ( 64 ). In addition to mitochondria, cytoplasmic NADPH oxidase (Nox) is the main source of cytoplasmic ROS ( 55 ).…”

Section: Oxidative Stress and Rosmentioning

confidence: 99%

The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications

et al. 2023

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Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia, with absolute insulin deficiency or insulin resistance as the main cause, and causes damage to various target organs including the heart, kidney and neurovascular. In terms of the pathological and physiological mechanisms of DM, oxidative stress is one of the main mechanisms leading to DM and is an important link between DM and its complications. Oxidative stress is a pathological phenomenon resulting from an imbalance between the production of free radicals and the scavenging of antioxidant systems. The main site of reactive oxygen species (ROS) production is the mitochondria, which are also the main organelles damaged. In a chronic high glucose environment, impaired electron transport chain within the mitochondria leads to the production of ROS, prompts increased proton leakage and altered mitochondrial membrane potential (MMP), which in turn releases cytochrome c (cyt-c), leading to apoptosis. This subsequently leads to a vicious cycle of impaired clearance by the body’s antioxidant system, impaired transcription and protein synthesis of mitochondrial DNA (mtDNA), which is responsible for encoding mitochondrial proteins, and impaired DNA repair systems, contributing to mitochondrial dysfunction. This paper reviews the dysfunction of mitochondria in the environment of high glucose induced oxidative stress in the DM model, and looks forward to providing a new treatment plan for oxidative stress based on mitochondrial dysfunction.

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Section: Oxidative Stress and Rosmentioning

confidence: 99%

The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications

et al. 2023

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“…Diabetic nephropathy (DN) is a serious microvascular complication of diabetes ( 1 ). On a global scale, the incidence of DN is on the rise in some regions ( 2 ), and it has become one of the main causes of renal failure.…”

Section: Introductionmentioning

confidence: 99%

Exploring the mechanisms underlying the therapeutic effect of the drug pair Rhubarb-Coptis in diabetic nephropathy using network pharmacology and molecular docking analysis

Wu¹,

Cao²,

Liu³

et al. 2022

Ann Transl Med

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Background: To use network pharmacology to explore the mechanism of the drug pair Rhubarb-Coptis in the treatment of diabetic nephropathy (DN).Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of drug pair Rhubarb-Coptis. Targets were obtained using the TCMSP and SwissTargetPrediction databases. DN disease targets were extracted from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Therapeutic Target database (TTD) databases. A "drug-compound-target" network and protein-protein interaction (PPI) network were constructed and analyzed through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed using AutoDock Vina and PyMOL software.Results: A total of 30 active components and 609 targets of Rhubarb-Coptis were screened out, and 98 common targets of DN and Rhubarb-Coptis were obtained. Quercetin, berberine, epiruberine, epautin, and moupinamide were the main active components in the treatment of DN. The STAT3, CTNNB1, PIK3R1, PIK3CA, and TP53 genes were identified as the potential 5 key targets. The GO enrichment analysis showed that these 5 key targets mainly involved in inflammation, oxidative stress, and apoptosis. KEGG enrichment analysis showed that the pathways were mainly enriched in the AGE-RAGE and HIF-1 signaling pathways.Molecular docking revealed that the 5 key targets could combine well with their corresponding active compounds.Conclusions: This study expounds the therapeutic effect of Rhubarb-Coptis on DN from a holistic perspective, and provides a valuable basis for clinical application and academic research.

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“…Clinical studies have shown that in nearly 2/3 of patients with DKD, there is varying degrees of tubular damage that occurs in the early stages of DKD and may play a key role in the progression of kidney disease [11]. Biomarkers of proximal tubular injury have been shown to correlate with DKD progression and are independent of traditional biomarkers of glomerular injury [12].These clinical and pathological data strongly suggest that tubular injury plays a key role in the development of DKD and may precede and interact with functional glomerular changes. Thus, glomerular and tubular injury are equally important in the progression of DKD.…”

Section: Discussionmentioning

confidence: 99%

Free Triiodothyronine predicts the risk of developing Diabetic Kidney Disease

Liu

et al. 2023

Preprint

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Purpose Low levels of Free Triiodothyronine (FT3) are associated with poor survival in chronic kidney disease, and the aim of this study was to further assess the relationship between changes in FT3 levels and renal damage in patients with type 2 diabetes based on glomerular and tubular markers. Methods We retrospectively studied 452 type 2 diabetic patients, measured glomerular damage markers (UACR, eGFR) and tubular damage markers (NAG/Cr,β2-MG), analyzed the relationship between FT3 and renal damage by logistic regression models, and plotted restrictive cubic splines. Results 41.6% of subjects had diabetic kidney disease (DKD), and the prevalence of DKD decreased progressively with increasing FT3 levels in the third quartile. Spearman correlation analysis showed that FT3 was negatively associated with UACR, NAG/Cr and β2-MG, while eGFR was positively associated with FT3. Multifactorial analysis, after adjusting for relevant confounders, revealed that compared with the lowest quartile of FT3, the highest quartile reduced the risk of developing urinary albumin (OR = 0.499,95% CI:0.289–0.856), moderate to severe impairment of glomerular filtration rate (OR = 0.106,95% CI:0.032–0.354), renal tubular marker β2 -MG positive (OR = 0.516,95% CI:0.299 to 0.883) and the risk of DKD occurrence (OR = 0.450,95% CI:0.260 to 0.774). In the sample model, FT3 levels below 4.39 pmol/L were associated with an increased risk of glomerular tubule injury and DKD occurrence. Conclusion FT3 is closely associated with glomerular tubular injury and is a protective factor. As FT3 levels (< 4.39 pmol/L) decrease, the risk of developing DKD becomes higher, and FT3 can be used as an independent predictor of developing DKD.

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Mitochondrial dysfunction in diabetic tubulopathy

Cited by 74 publications

References 124 publications

The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications

The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications

Exploring the mechanisms underlying the therapeutic effect of the drug pair Rhubarb-Coptis in diabetic nephropathy using network pharmacology and molecular docking analysis

Free Triiodothyronine predicts the risk of developing Diabetic Kidney Disease

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