Autophagy Dysregulation in Diabetic Kidney Disease: From Pathophysiology to Pharmacological Interventions

Cells, Journal Year: 2021, Volume and Issue: 10(9), P. 2497 - 2497

Published: Sept. 21, 2021

Diabetic kidney disease (DKD) is a frequent, potentially devastating complication of diabetes mellitus. Several factors are involved in its pathophysiology. At cellular level, diabetic associated with many structural and functional alterations. Autophagy mechanism that transports intracytoplasmic components to lysosomes preserve function homeostasis. integrity essential for cell homeostasis, alteration can drive damage or death. profound autophagy dysregulation. rate flux alterations were described several models disease. Some them closely linked progression severity. antidiabetic agents have shown significant effects on autophagy. A few also demonstrated modify improved outcomes affected patients. Other drugs target being explored clinical use patients The modulation could be relevant the pharmacological treatment prevention this future. Therefore, an evolving area requires further experimental research. Here we discuss relationship between potential value as intervention.

Language: Английский

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Renal fibrosis as a hallmark of diabetic kidney disease: potential role of targeting transforming growth factor-beta (TGF-β) and related molecules

Expert Opinion on Therapeutic Targets, Journal Year: 2022, Volume and Issue: 26(8), P. 721 - 738

Published: Aug. 3, 2022

Diabetic kidney disease (DKD) is the most common cause of end-stage renal (ESRD) worldwide. Currently, there no effective treatment to completely prevent DKD progression ESRD. Renal fibrosis and inflammation are major pathological features DKD, being pursued as potential therapeutic targets for DKD.Inflammation involved in pathogenesis DKD. Anti-inflammatory drugs have been developed combat but without efficacy demonstrated. Thus, we focused on mechanisms TGF-β-induced well discussing important molecules influencing TGF-β signaling pathway their development into new pharmacotherapies, rather than targeting ligand and/or its receptors, such options include Smads, microRNAs, histone deacetylases, connective tissue growth factor, bone morphogenetic protein 7, hepatocyte cell division autoantigen 1.TGF-β a critical driver Molecules that modulate itself potentially superior safely A comprehensive elucidation important, which requires better model system access clinical samples via collaboration between basic researchers.

Language: Английский

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Role of sex hormones in diabetic nephropathy

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: April 18, 2023

Diabetic nephropathy (DN) is the most common microvascular complication in diabetes and one of leading causes end-stage renal disease. The standard treatments for patients with classic DN focus on blood glucose pressure control, but these can only slow progression instead stopping or reversing In recent years, new drugs targeting pathological mechanisms (e.g., blocking oxidative stress inflammation) have emerged, therapeutic strategies are gaining increasing attention. A growing number epidemiological clinical studies suggest that sex hormones play an important role onset DN. Testosterone main hormone males thought to accelerate occurrence Estrogen females renoprotective effects. However, underlying molecular mechanism by which regulate has not been fully elucidated summarized. This review aims summarize correlation between evaluate value hormonotherapy

Language: Английский

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PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury

Cellular Signalling, Journal Year: 2024, Volume and Issue: 121, P. 111282 - 111282

Published: July 5, 2024

Language: Английский

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Novel Biomarkers for the diagnosis of diabetic nephropathy.

PubMed, Journal Year: 2024, Volume and Issue: 15(3), P. 382 - 391

Published: Jan. 1, 2024

Diabetes mellitus and its complications are a known public health problem nowadays. Diabetic nephropathy is one of the main result multiple mechanisms, including: activation renin-angiotensin-aldosterone system, formation advanced glycation end products chronic inflammation that led to glomerular tubulo-interstitial damage producing mesangial expansion glomerulosclerosis, which finally results in kidney disease. Early detection diabetic essential for adequate intervention stop, or at least slow down progression. Multiple markers have been described, not only classic ones such as serum creatinine, urea, albuminuria, but this point also novel biomarkers neutrophil gelatinase-associated lipocalin, tumor necrosis factor 1 receptor monocyte chemoattractant protein-1, among others. The aim article was provide an update review role diagnosis nephropathy.

Language: Английский

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pdx1 Knockout Leads to a Diabetic Nephropathy– Like Phenotype in Zebrafish and Identifies Phosphatidylethanolamine as Metabolite Promoting Early Diabetic Kidney Damage

Diabetes, Journal Year: 2022, Volume and Issue: 71(5), P. 1073 - 1080

Published: Jan. 31, 2022

The pdx1−/− zebrafish mutant was recently established as a novel animal model of diabetic retinopathy. In this study, we investigate whether knockout pdx1 also leads to kidney disease (DKD). larvae exhibit several signs early DKD, such glomerular hypertrophy, impairments in the filtration barrier corresponding microalbuminuria, and basement membrane (GBM) thickening. Adult mutants show progressive GBM thickening comparison with larval state. Heterozygous hypertrophy initial establishment DKD similar larvae. RNA sequencing adult pdx1+/− kidneys uncovered regulations multiple expected pathways related podocyte disruption hinting at vascular dysregulation without obvious morphological alterations. Metabolome analysis pharmacological intervention experiments revealed contribution phosphatidylethanolamine damage. conclusion, study identified for showing progression already stage selective features later mutants.

Language: Английский

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Comparative safety of sodium-glucose co-transporter 2 inhibitors in elderly patients with type 2 diabetes mellitus and diabetic kidney disease: a systematic review and meta-analysis

Renal Failure, Journal Year: 2023, Volume and Issue: 45(1)

Published: May 29, 2023

The safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with diabetic kidney disease (DKD) is still controversial. This study aimed to analyze the SGLT2 type diabetes mellitus (T2DM) and DKD. We systematically searched PubMed, Embase, Web Science, Cochrane Library from inception March 2023. Randomized controlled trials (RCTs) were included. Data including patient characteristics interesting outcomes extracted, dichotomous data continuous variables evaluated using risk ratio (RR) 95% confidence intervals (CIs) mean difference (MD) CIs, respectively. A total 14 RCTs 59874 participants finally There 38,252 males (63.9%) 21,622 females (36.1%). patients' age was > 64.6 years. could delay further decline estimated glomerular filtration rate (eGFR) when eGFR ≥ 60 ml/min/1.73m2 (MD: 2.36; 95%CI [1.15–3.57]). < (RR: 0.86; [0.67–1.11]) may have a relatively increased acute injury compared ml/min/1.73m2. incidence genital mycotic infections 3.47; [2.97–4.04]) ketoacidosis 2.25; [1.57–3.24]). Except for ketoacidosis, other adverse reactions few, indicating that are safe T2DM Safety renoprotection be diminished used

Language: Английский

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The effects of Salvia miltiorrhiza and ligustrazine injection combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis

Medicine, Journal Year: 2024, Volume and Issue: 103(8), P. e35853 - e35853

Published: Feb. 23, 2024

In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different studies have reported conflicting results. Therefore, a systematic review meta-analysis necessary to assess the efficacy safety of SML treatment DKD.

Language: Английский

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LncRNA SNHG16 regulates RAS and NF-κB pathway-mediated NLRP3 inflammasome activation to aggravate diabetes nephropathy through stabilizing TLR4

Acta Diabetologica, Journal Year: 2023, Volume and Issue: 60(4), P. 563 - 577

Published: Jan. 20, 2023

Language: Английский

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Polyphenols-rich polyherbal mixture attenuates hepatorenal impairment, dyslipidaemia, oxidative stress and inflammation in alloxan-induced diabetic rats

Journal of Applied Animal Research, Journal Year: 2023, Volume and Issue: 51(1), P. 515 - 523

Published: July 5, 2023

Effects of polyherbal mixture on hepatorenal injury and dyslipidaemia in alloxan-induced diabetic rats were evaluated. Alloxan monohydrate (120 mg/kg, i.p.) was injected into Wistar to induce diabetes. Animals allotted six groups (n = 6) treatments administered for consecutive weeks as normal controls, glibenclamide (200, 400 600 mg/kg), respectively. Ameliorative effects the investigated by assessing FBG levels, changes body organ (liver kidney) weights, biochemical parameters, oxidative stress along with inflammatory parameters addition histopathological examination liver kidney. The results showed that alloxan-injected had significant (P < 0.05) hyperglycaemia elevated serum levels indices (ALT, AST, ALP, bilirubin, total protein, albumin, creatinine, BUN uric acid) hyperlipidaemia evidenced increased TC, TG, LDL-C, VLDL-C decreased HDL-C levels. Furthermore, diabetes induction caused an increase lipid peroxidation (MDA) a reduction antioxidant markers (SOD CAT activities) well inflammation (TNF-α) hepatic renal tissues. Polyherbal remarkably improved aforementioned dose-dependent manner. Histopathological findings supported results. Conclusively, this study has provided novel insights efficacy mixtures managing its secondary complications mellitus.

Language: Английский

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