P0970EXOSOMAL MIR-92A-1-5P DERIVED FROM PROXIMAL TUBULAR EPITHELIAL CELLS INDUCES EPITHELIAL-MESENCHYMAL TRANSITION IN MESANGIAL CELLS IN DIABETIC NEPHROPATHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yi-Chun Tsai ◽  
Mei-Chuan Kuo ◽  
Ya-Ling Hsu
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mesangial Cells ◽  
Normal Individual ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Mesenchymal Transition ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Type 2 Diabetic

Abstract Background and Aims Diabetic nephropathy (DN) has been the leading cause of end-stage renal disease in the world-wide. Exosomes play a key role in signal transduction between cell-cell communication in kidney pathophysiology. The aim of this study is to investigate that HK-2 cells-derived exosomal miR-92a-1-5p causes epithelial-mesenchymal transition (EMT) in mesangial cells (MCs), further leading to DN progression. Method The function of HK-2 cells-derived exosomes under normal glucose (NG) and high glucose (HG) was analyzed in mouse MCs model. Total RNAs were extracted from renal proximal tubular epithelial cells (RPTECs) of normal individual and type 2 diabetes for small RNA expression profiling using next-generation sequencing (NGS), then analyzed using systematic bioinformatics analyses. The expression of miR-92a-1-5p was examined in HK-2 cells-derived exosomes and MCs treated with HK-2 cells-derived exosomes under HG. The role of miR-92a-1-5p in EMT was evaluated using MCs model under NG and HG conditions. Urinary exosomal miR-92a-1-5p levels were measured in 50 type 2 diabetic patients and 34 healthy volunteers who were enrolled to determine the relationship between urinary exosomal miR-92a-1-5p and kidney function. Results Decreased E-cadherin, and increased N-cadherin and Vimentin expression were found in mouse MCs treated with HK-2 cells-derived exosomes under HG. Transcriptome analysis of RPTECs of normal individual and type 2 diabetic patient indicated that miR-92a-1-5p contributes to HG-induced renal proliferation. HG elevated miR-92a-1-5p expression in HK-2 cells and exosomes derived from-HK-2 cells, at meanwhile exosomal miR-92a-1-5p derived from-HK-2 cells under HG leads to EMT in mouse MCs. miR-92a-1-5p mimic increased EMT in mouse MCs under NG, and miR-92a-1-5p inhibitor reversed EMT in mouse MCs induced by exosomes derived from HK-2 cells under HG. EMT of mouse MCs was enhanced in the presence of exosomes isolated from the urine of type 2 diabetic patients with high levels of exosomal miR-92a-1-5p. Type 2 diabetic patients had higher urinary exosomal miR-92a-1-5p levels than normal individuals. Higher urinary exosomal miR-92a-1-5p levels were significantly correlated with lower renal function and higher albuminuria in human model. Conclusion Exosomal miR-92a-1-5p derived from HK-2 cells under HG induces EMT in mesangial cells. Blocking miR-92a-1-5p epigenetic regulatory network might be a potential therapeutic strategy to prevent EMT in DN.

scholarly journals Autocrine Exosomal Fibulin-1 as a Target of MiR-1269b Induces Epithelial–Mesenchymal Transition in Proximal Tubule in Diabetic Nephropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yi-Chun Tsai ◽  
Wei-Wen Hung ◽  
Wei-An Chang ◽  
Ping-Hsun Wu ◽  
Ling-Yu Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Mesenchymal Transition ◽  
Cell Communication ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Mesenchymal Transition ◽  
Type 2 Diabetic

Background: Diabetic nephropathy (DN) is an increasing threat to human health and is regarded to be the leading cause of end-stage renal disease worldwide. Exosomes deliver biomolecule massages and may play a key role in cell communication and the progression of DN.Methods: A cross-disciplinary study, including in vivo, in vitro, and human studies, was conducted to explore the cross-talk within proximal tubular epithelial cells (PTECs) in DN. Exosomal protein from PTECs treated with high glucose (HG) was purified and examined using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Next-generation sequencing (NGS) was utilized to analyze RNAs extracted from PTECs from a type 2 diabetic patient and a normal individual. HK-2 cells were used to assess exosomal protein and its modulation and biofunction in DN. Normal individuals and type 2 diabetic patients were enrolled, and nondiabetic db/m mice and diabetic db/db mice were used to validate the molecular mechanism of exosomes in DN.Results: HG stimulated PTECs to increase Fibulin-1 (FBLN1) expression, and PTECs secreted FBLN1 through exosome delivery, thereby inducing epithelial–mesenchymal transition (EMT) in PTECs. Transcriptome analysis found that FBLN1 expression was modulated by miR-1269b, which was downregulated by HG in HK-2 cells. While transfection of miR-1269b reversed FBLN1-mediated EMT in PTECs, miR-1269b inhibitor modulated the phenotype of PTECs toward mesenchymal type under normal glucose (NG) condition. Most importantly, urinary FBLN1 and exosomal miR-1269b levels were correlated with the severity of kidney injury in type 2 diabetic patients.Conclusion: This study demonstrated the communication within PTECs through exosome transmission in an autocrine pattern. MiR-1269b–FBLN1 epigenetic regulatory network could be a potential therapeutic strategy to prevent the progression of DN.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial

2020 ◽  
pp. 1-10
Author(s):  
Giuseppe Derosa ◽  
Angela D’Angelo ◽  
Chiara Martinotti ◽  
Maria Chiara Valentino ◽  
Sergio Di Matteo ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Metabolic Control ◽  
Vitamin D3 ◽  
Therapy Group ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Abstract. Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

Evaluation of aortic arch calcification in type 2 diabetic patients

VASA ◽  
2005 ◽  
Vol 34 (2) ◽  
pp. 113-117 ◽  
Author(s):  
Papanas ◽  
Symeonidis ◽  
Maltezos ◽  
Giannakis ◽  
Mavridis ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Aortic Arch ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Insulin Dependence ◽  
Artery Disease ◽  
Type 2 Diabetic ◽  
Aortic Arch Calcification

Background: The purpose of this study is to evaluate the severity of aortic arch calcification among type 2 diabetic patients in association with diabetes duration, diabetic complications, coronary artery disease and presence of cardiovascular risk factors. Patients and methods: This study included 207 type 2 diabetic patients (101 men) with a mean age of 61.5 ± 8.1 years and a mean diabetes duration of 13.9 ± 6.4 years. Aortic arch calcification was assessed by means of posteroanterior chest X-rays. Severity of calcification was graded as follows: grade 0 (no visible calcification), grade 1 (small spots of calcification or single thin calcification of the aortic knob), grade 2 (one or more areas of thick calcification), grade 3 (circular calcification of the aortic knob). Results: Severity of calcification was grade 0 in 84 patients (40.58%), grade 1 in 64 patients (30.92%), grade 2 in 43 patients (20.77%) and grade 3 in 16 patients (7.73%). In simple regression analysis severity of aortic arch calcification was associated with age (p = 0.032), duration of diabetes (p = 0.026), insulin dependence (p = 0.042) and presence of coronary artery disease (p = 0.039), hypertension (p = 0.019), dyslipidaemia (p = 0.029), retinopathy (p = 0.012) and microalbuminuria (p = 0.01). In multiple regression analysis severity of aortic arch calcification was associated with age (p = 0.04), duration of diabetes (p = 0.032) and presence of hypertension (p = 0.024), dyslipidaemia (p = 0.031) and coronary artery disease (p = 0.04), while the association with retinopathy, microalbuminuria and insulin dependence was no longer significant. Conclusions: Severity of aortic arch calcification is associated with age, diabetes duration, diabetic complications (retinopathy, microalbuminuria), coronary artery disease, insulin dependence, and presence of hypertension and dyslipidaemia.

The Effect of Insulin Treatment on the Balance between Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Type 2 Diabetic Patients

1992 ◽  
Vol 68 (03) ◽  
pp. 253-256 ◽  
Author(s):  
Thomas Vukovich ◽  
Sylvia Proidl ◽  
Paul Knöbl ◽  
Harald Teufelsbauer ◽  
Christoph Schnack ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Insulin Treatment ◽  
Plasminogen Activator Inhibitor ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type 2 Diabetic Patients ◽  
Glycemic Regulation ◽  
Type 2 Diabetic ◽  
Pai 1

SummaryBeside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40). In conclusion, our results indicate that insulin treatment associated with metabolic improvement has no adverse effect to fibrinolysis in type 2 diabetic patients.

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