With aging, the kidney undergoes inexorable and progressive changes in structural and functional performance. These aging-related alterations are more obvious and serious in diabetes mellitus (DM). Renal accelerated aging under DM conditions is associated with multiple stresses such as accumulation of advanced glycation end products (AGEs), hypertension, oxidative stress, and inflammation. The main hallmarks of cellular senescence in diabetic kidneys include cyclin-dependent kinase inhibitors, telomere shortening, and diabetic nephropathy-associated secretory phenotype. Lysosome-dependent autophagy and antiaging proteins Klotho and Sirt1 play a fundamental role in the accelerated aging of kidneys in DM, among which the autophagy-lysosome system is the convergent mechanism of the multiple antiaging pathways involved in renal aging under DM conditions. Metformin and the inhibitor of sodium–glucose cotransporter 2 are recommended due to their antiaging effects independent of antihyperglycemia, besides angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Additionally, diet intervention including low protein and low AGEs with antioxidants are suggested for patients with diabetic nephropathy (DN). However, their long-term benefits still need further study. Exploring the interactive relationships among antiaging protein Klotho, Sirt1, and autophagy-lysosome system may provide insight into better satisfying the urgent medical needs of elderly patients with aging-related DN.
#1Judit Hodrea(MTA: Hungarian Academy of Sciences)H-Index: 9
#2Dora Balogh(MTA: Hungarian Academy of Sciences)H-Index: 7
Last. Attila Szabo(MTA: Hungarian Academy of Sciences)H-Index: 59
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Diabetic kidney disease is a worldwide epidemic and therapies are incomplete. Clinical data suggest that improved renal outcomes by SGLT2i are partly beyond their antihyperglycemic effects, however the mechanisms are still elusive. Here we investigated the effect of SGLT2i dapagliflozin (DAPA) in the prevention of elevated O-GlcNAcylation and tubular hypoxia as contributors of renal fibrosis. Type 1 diabetes was induced by streptozotocin in adult male Wistar rats. After the onset of diabetes, ra...
#1Jiang Xu(USTC: University of Science and Technology of China)H-Index: 2
#2Lin-Qing Liu(USTC: University of Science and Technology of China)H-Index: 2
Last. Shandong Ye(USTC: University of Science and Technology of China)H-Index: 2
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Diabetic nephropathy (DN) is the major microvascular complication of diabetes mellitus and the most important cause of end-stage renal disease worldwide. Metformin is the preferred oral hypoglycaemic drug for type 2 diabetes mellitus (T2DM). Recent studies have shown that besides lowering blood glucose, metformin also has protective effects on renal function, but its mechanism is not clear. In this study, we established a diabetic rat model by high-fat feeding combined with intraperitoneal injec...
: High glucose (HG)-induced endothelial senescence and dysfunction contribute to the increased cardiovascular risk in diabetes. Empagliflozin, a selective sodium glucose co-transporter2 (SGLT2) inhibitor, reduced the risk of cardiovascular mortality in type 2 diabetic patients but the protective mechanism remains unclear. This study examines the role of SGLT2 in HG-induced endothelial senescence and dysfunction. Porcine coronary artery cultured endothelial cells (ECs) or segments were exposed to...
#2Ying Shao(PRC: China Medical University (PRC))H-Index: 9
Last. Qiuyue Wang(PRC: China Medical University (PRC))H-Index: 13
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Abstract Metformin, as the basic pharmacological therapy and the first preventive drug in type 2 diabetes mellitus (T2DM), is proved to have potential protection in diabetic kidney disease (DKD). Here, we established a diabetic rat model induced by high-fat diet and low dose streptozotocin, and high glucose cultured rat mesangial cells (RMCs) pre-treated with metformin or transfected with AMPK, SIRT1 and FoxO1 small interfering RNA, and detected oxidative stress and autophagy related factors to ...
Last. Csaba P. Kovesdy(UTHSC: University of Tennessee Health Science Center)H-Index: 102
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Abstract The FDA has recently endorsed metformin use in patients with T2D and stage 3 CKD (CKD3). However, metformin safety in elderly individuals is unknown. The aim of this study was to identify frequency and risk factors of lactic acid (LA) elevation in ambulatory elderly male US veterans with stable diabetic CKD3 treated with metformin. We studied 92 patients with non-diabetic CKD3 (Group1), diabetic CKD3 not on metformin (Group2) and diabetic CKD3 on metformin (Group 3). Mean LA levels were...
#1Chia-Ter Chao(NTU: National Taiwan University)H-Index: 18
#2Jui Wang(NTU: National Taiwan University)H-Index: 9
Last. Kuo-Liong Chien(NTU: National Taiwan University)H-Index: 62
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To examine the effect of frailty on diabetic kidney disease patients’ risk of progression to end-stage renal disease (ESRD), mortality, and adverse episodes, as whether frailty modifies their risk of developing ESRD and other adverse outcomes remains unclear. We identified 165,461 DKD patients from the Longitudinal Cohort of Diabetes Patients in Taiwan (n=840,000) between 2004 and 2010, classifying them into those without frailty or with 1, 2 and ≥3 frailty components based on a modified version...
Last. Yueze Liu(Shanxi Medical University)H-Index: 1
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: Incretin contains two peptides named glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Drug therapy using incretin has become a new strategy for diabetic treatments due to its significant effects on improving insulin receptors and promoting insulinotropic secretion. Considering the fact that diabetes millitus is a key risk factor for almost all age-related diseases, the extensive protective roles of incretin in chronic diseases have received great attention...
Last. Rosa Fernandes(UC: University of Coimbra)H-Index: 28
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Abstract Aims Oxidative stress has been linked to the development and progression of diabetic nephropathy (DN). The present study evaluated whether the dipeptidyl peptidase-4 inhibitor sitagliptin attenuates glomerular lesions and oxidative stress evoked by chronic hyperglycemia, by a mechanism independent of insulin secretion and glycemia normalization. Main methods A rat model of DN caused by streptozotocin injection was established and the effects of sitagliptin (5 mg/kg/day) were evaluated a...
Abstract Background Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + ...
BACKGROUND: Emerging evidence demonstrates the involvement of Janus tyrosine kinase/signal transducer and transcription activator (JAK/STAT) proteins in the pathophysiology of diabetic kidney disease (DKD). The JAK/STAT pathway is involved in the inflammatory response and endothelial cell dysfunction observed in DKD. The glucagon-like peptide-1 (GLP-1) analog liraglutide is an effective treatment for type 2 diabetes because it improves the inflammatory changes observed in experimental models of ...
Last. Zheng-xin Xu(YZU: Yangzhou University)H-Index: 1
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Abstract Ethnopharmacological relevance Huangkui capsule (HKC), extracted from Abelmoschus manihot (L.) medic (AM), as a patent proprietary Chinese medicine on the market for approximately 20 years, has been clinically used to treat chronic glomerulonephritis. Renal fibrosis has been implicated in the onset and development of diabetic nephropathy (DN). However, the potential application of HKC for preventing DN has not been evaluated. Aim of the study This study was designed to investigate the e...
Cellular senescence is a cell fate that occurs in response to numerous types of stress and can promote tissue repair or drive inflammation and disruption of tissue homeostasis depending on the context. Aging and obesity lead to an increase in the senescent cell burden in multiple organs. Senescent cells release a myriad of senescence-associated secretory phenotype factors that directly mediate pancreatic β-cell dysfunction, adipose tissue dysfunction, and insulin resistance in peripheral tissues...
The aging process leads to progressive loss of kidney function. Sirtuin1 (SIRT1) exerts renoprotective effects by conferring resistance to cellular stresses. Trehalose potentially displayed various beneficial effects to promote health span. In this study, we investigated the effects of trehalose on renal SIRT1 and kidney function in senescent rats. Trehalose (2% w/v) was administrated in drinking water for 1 month to male aged rats (24 months). Then, the level of SIRT1 mRNA and protein, malondia...
Background and Objectives: Glycated hemoglobin (HbA1c) dosage is considered the gold standard in glycol-metabolic monitoring, but it presents limits, which can underestimate the glycemia trend. In this regard, it was introduced the glycated albumin (GA). The aim of the study is to verify the predictivity of the GA compared to HbA1c in identifying glyco-metabolic alterations in non-diabetic and diabetic hemodialysis (HD) patients. Materials and Methods: For this purpose, we conducted a multicente...
Introduction null The clinical-histologic correlation in diabetic nephropathy is not completely known. null null null Methods null We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). null null null Results null Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% 10% to 20% of the sample. Moderate hyalinosis a...
Last. Yaoming Xue(Southern Medical University)H-Index: 15
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BACKGROUND Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and results in serious public health problems. Although a great number of studies have been performed to elucidate the mechanisms of this disease, these mechanisms remain largely unknown. METHODS Cell and animal models were first constructed using human renal proximal tubule cells stimulated by high glucose (HG) and mice induced by streptozotocin (STZ). After Klotho overexpression, Klotho expression was asses...
Last. Suxian Zhou(GLMU: Guilin Medical University)H-Index: 2
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Background Diabetic nephropathy (DN) is one of the main complications of diabetes mellitus (DM), which leads to the long-term loss of kidney functions. Long noncoding RNAs (LncRNAs) can alleviate DN by interacting with microRNAs (miRNAs). In this work, we aimed to explore the effects of the MALAT1/miR-200c/NRF2 regulatory axis on the pyroptosis and oxidative stress (Oxidative stress, OS) of renal podocytes in high glucose (HG) environment and whether the lipid-lowering drug atorvastatin (AT) can...
Klotho was initially introduced as an antiaging molecule. Klotho deficiency significantly reduces lifespan, and its overexpression extends it and protects against various pathological phenotypes, especially renal disease. It was shown to regulate phosphate and calcium metabolism, protect against oxidative stress, downregulate apoptosis, and have antiinflammatory and antifibrotic properties. The course of diabetes mellitus and diabetic nephropathy resembles premature cellular senescence and cause...
