Nephropathy in Type II diabetes

Summary: The incidence and prevalence of end-stage renal failure due to renal involvement in patients with type II diabetes has increased in the Western world and in Asia. Interesting differences of prevalence of this disease are found between nations. the reasons for the increase in the frequency of nephropathy in type II diabetes include: (i) an increasing prevalence of type II diabetes; (ii) ageing of the population; and (iii) improved survival of patients with type II diabetes. Today patients frequently live long enough to develop diabetic nephropathy. In contrast with previous opinion, no major differences in renal involvement is found between type I and type II diabetes. This applies to renal haemodynamics as well as renal histology, although non-specific changes, presumably of an ischaemic nature are more frequently found in patients with type II diabetes. the renal risk appears to be similar in type II diabetes (i.e. cumulative prevalence of proteinuria and rate of progression to renal failure).     

Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy

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Activation of Hypoxia-Inducible Factors Prevents Diabetic Nephropathy

Hyperglycemia results in increased oxygen consumption and decreased oxygen tension in the kidney. We tested the hypothesis that activation of hypoxia-inducible factors (HIFs) protects against diabetes-induced alterations in oxygen metabolism and kidney function. Experimental groups consisted of control and streptozotocin-induced diabetic rats treated with or without chronic cobalt chloride to activate HIFs. We elucidated the involvement of oxidative stress by studying the effects of acute administration of the superoxide dismutase mimetic tempol. Compared with controls, diabetic rats displayed tissue hypoxia throughout the kidney, glomerular hyperfiltration, increased oxygen consumption, increased total mitochondrial leak respiration, and decreased tubular sodium transport efficiency. Diabetic kidneys showed proteinuria and tubulointerstitial damage. Cobalt chloride activated HIFs, prevented the diabetes-induced alterations in oxygen metabolism, mitochondrial leak respiration, and kidney function, and reduced proteinuria and tubulointerstitial damage. The beneficial effects of tempol were less pronounced after activation of HIFs, indicating improved oxidative stress status. In conclusion, activation of HIFs prevents diabetes-induced alteration in kidney oxygen metabolism by normalizing glomerular filtration, which reduces tubular electrolyte load, preventing mitochondrial leak respiration and improving tubular transport efficiency. These improvements could be related to reduced oxidative stress and account for the reduced proteinuria and tubulointerstitial damage. Thus, pharmacologic activation of the HIF system may prevent development of diabetic nephropathy.     

氧化应激与糖尿病性勃起功能障碍

勃起功能障碍(ED)是糖尿病进程中常见的并发症,其发病机制十分复杂,涉及到神经及神经递质、血管及血管活性物质、内分泌、代谢等多方面因素。糖尿病状态下,自由基增多引发氧化应激损伤,影响到糖尿病性ED发生发展中的各个环节。本文针对氧化应激在糖尿病性勃起功能障碍进程中的作用作一综述。     

Use of Alpha-Lipoic Acid in Prevention of Contrast-Induced Nephropathy in Diabetic Patients

In this prospective study, we aimed to determine the protective antioxidant role of alpha-lipoic acid (ALA) on development of contrast-induced nephropathy (CIN) in diabetic patients undergoing coronary angiography. Seventy-eight diabetic patients undergoing coronary angiography were included. Thirty-nine patients were randomized to control group and 39 patients to ALA group. Both groups were hydrated on the day of angiography, and the ALA group had also received three doses of “Thioctacid 600 mg HR, MEDA Manufacturing GmbH” in pill form. Serum creatinine clearance, cystatin C, and urinary neutrophil gelatinase-associated lipocalin (NGAL) were studied before and after angiography. We defined CIN as either ≥25% or ≥0.5 mg/dL increase in serum creatinine at 48th hour after angiography. Baseline clinical characteristics were similar in both groups. Mehran risk score and creatinine clearance were comparable in control and therapy groups (5.59 ± 1.96 vs. 5.49 ± 1.73, p = 0.54 and 89 ± 21 vs. 96 ± 24, p = 0.13, respectively). The volumes of contrast media (median values of 80 mL vs. 75 mL) and hydration with saline (2862 ± 447 mL vs. 2637 ± 592 mL) were also similar (p > 0.05). The incidence of CIN was the same (8%) in both the groups. Alterations in serum creatinine, cystatin C, and urinary NGAL levels before and after the procedure were comparable between the ALA and control groups (group p-values were >0.05 in two-way repeated measures analysis of variance). We presented for the first time that ALA therapy added to hydration does not decrease the risk of CIN development in diabetic patients undergoing coronary angiography.     

2型糖尿病肾病大鼠模型的建立

目的：建立2型糖尿病肾病（DIN）大鼠模型。方法：雌性SD大鼠接受单侧肾切除手术2周后，给予高糖高脂饮食（常规饲料加20％蔗糖、10％猪油、2．5％胆固醇）喂养4周，再加用小剂量链脲佐菌素（蜘亿，30mg／kg）腹腔注射，分别检测1周、7周后各组大鼠血糖、胰岛素、血压、血脂、尿蛋白、肾功能等指标，并于7周后进行组织形态学观察。结果：单侧肾切除大鼠给予高糖高脂饮食和低剂量STZ观察7周后，模型成功动物具有高血糖、高血脂、高血压、胰岛素抵抗等特点，并出现DN相应的形态及功能改变。结论：通过单侧肾切除后，饮食加小剂量蜘亿的方法，可成功制备2型DN大鼠模型。     

治糖保肾冲剂治疗早期糖尿病肾病疗效观察

目的 :观察治糖保肾冲剂治疗早期糖尿病肾病的疗效。方法 :采用随机、对照法研究治糖保肾冲剂的临床疗效。结果 :苯那普利组可降低患者尿白蛋白排泄率 ,治糖保肾冲剂加苯那普利组在中医症状改善、降低血糖、减少尿白蛋白排泄率方面均优于苯那普利组 (P <0 .0 5 ,0 .0 1)。结论 :治糖保肾冲剂对糖尿病肾病有明显的疗效。     

Oxidation Flux Change on Glomerulus Membrane in Normal and Diabetic Nephropathy

The oxidation process is one of the most important natural processes. Oxidative change in diabetes is believed to be an important process in the pathogenesis. Here, the author determines the oxidation flux change in diabetic nephropathy. A simulation test to determine the oxidation flux change based on nano medicine technique is used. An increase in oxidation flux in the diabetic nephropathy can be derived. Therefore, this work can support the finding that the oxidation flux change plays an important role in the pathogenesis of diabetic nephropathy. Conclusively, the oxidative stress can bring glomerulus thickness, and the thickness glomerulus can further amplify the oxidative injuries.     

Disruption of Renal Tubular Mitochondrial Quality Control by Myo-Inositol Oxygenase in Diabetic Kidney Disease

Diabetic kidney disease (DKD) is associated with oxidative stress and mitochondrial injury. Myo-inositol oxygenase (MIOX), a tubular-specific enzyme, modulates redox imbalance and apoptosis in tubular cells in diabetes, but these mechanisms remain unclear. We investigated the role of MIOX in perturbation of mitochondrial quality control, including mitochondrial dynamics and autophagy/mitophagy, under high-glucose (HG) ambience or a diabetic state. HK-2 or LLC-PK1 cells subjected to HG exhibited an upregulation of MIOX accompanied by mitochondrial fragmentation and depolarization, inhibition of autophagy/mitophagy, and altered expression of mitochondrial dynamic and mitophagic proteins. Furthermore, dysfunctional mitochondria accumulated in the cytoplasm, which coincided with increased reactive oxygen species generation, Bax activation, cytochrome C release, and apoptosis. Overexpression of MIOX in LLC-PK1 cells enhanced the effects of HG, whereas MIOX siRNA or d-glucarate, an inhibitor of MIOX, partially reversed these perturbations. Moreover, decreasing the expression of MIOX under HG ambience increased PTEN-induced putative kinase 1 expression and the dependent mitofusin-2–Parkin interaction. In tubules of diabetic mice, increased MIOX expression and mitochondrial fragmentation and defective autophagy were observed. Dietary supplementation of d-glucarate in diabetic mice decreased MIOX expression, attenuated tubular damage, and improved renal functions. Notably, d-glucarate administration also partially attenuated mitochondrial fragmentation, oxidative stress, and apoptosis and restored autophagy/mitophagy in the tubular cells of these mice. These results suggest a novel mechanism linking MIOX to impaired mitochondrial quality control during tubular injury in the pathogenesis of DKD and suggest d-glucarate as a potential therapeutic agent for the amelioration of DKD.     

糖尿病氧化应激与勃起功能障碍的关系

ED是糖尿病进程中发病率较高的并发症。糖尿病可引发氧化应激,氧化应激通过对血管内皮、周围神经、阴茎平滑肌功能的影响和引发细胞凋亡等机制在糖尿病性ED的发病进程中起重要作用。现就氧化应激与糖尿病性ED关系的研究进展作一综述。