Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy

Adiponectin, a novel adipose-derived adipocytokine, has beneficial effects not only on improvement of insulin sensitivity but also on mitigation of vascular damage. To evaluate whether adiponectin is implicated in the pathogenesis of diabetic nephropathy characterized by microvascular damage, we examined urinary and serum adiponectin levels in type 2 diabetic patients with different stages of nephropathy. We first confirmed adiponectin is excreted into urine through Western blot analysis, followed by measurements of urinary and serum adiponectin levels by radioimmunoassay. Interestingly, urinary adiponectin excretion levels were markedly increased in patient group with overt nephropathy relative to the groups without nephropathy and with incipient nephropathy. Surprisingly, serum adiponectin levels were also elevated in patient group with overt nephropathy. Increased urinary adiponectin excretion may result from elevations in circulating adiponectin levels and enhanced filtration of circulating adiponectin through the damaged kidney. Furthermore, adiponectin synthesis in adipose tissue and its secretion into circulating blood may be enhanced to mitigate microvascular damage in the advanced stage of diabetic nephropathy.     

Progression of early phase diabetic nephropathy in streptozotocin-induced diabetic rats: evaluation of various kidney-related parameters

Diabetic nephropathy (DN) is one of the serious secondary complications of diabetes, which results in end-stage renal failure. Reports on the progressive nature of early phase DN especially with respect to kidney parameters such as kidney weight, type IV collagen excretion, total kidney and urinary glycosaminoglycans (GAGs) are few. This work was undertaken to determine systematically the progression of early phase DN in relation to various kidney-related parameters for a period of four months. Experimentally-induced diabetic rats were grouped based on fasting blood glucose levels. Various basic and kidney-related parameters such as kidney weight, microalbuminuria, urinary excretion of GAGs and type IV collagen, total kidney GAGs, histopathology, glomerular area and glomerular volume were examined in control and diabetic rats. There was a progressive increase in fasting blood sugar, urine sugar, kidney weight, microalbuminuria, urine glycosaminoglycans, urine type IV collagen, glomerular area and glomerular volume but there was a progressive decrease in kidney glycosaminoglycans. Glomerular sclerotic condition was aggravated with the increase in duration of diabetes from 1 to 4 months. Onset of DN in rats begins subtly after one month of diabetes but gets vitiated and more pronounced at the end of four months.     

Progesterone profile in buffaloes during various stages of oestrous cycle using radioimmunoassy technique

Investigation were carried out to study the norms of progesterone concentration in the blood serum of buffaloes during various phases of oestrous cycle. Twenty four animals (12 heifers and 12 cows) were used. The blood serum samples were stored at -20 degrees C until processed for progesterone assay. The progesterone concentrations were measured by the radioimmunoassay technique. The progesterone levels were 0.360 +/- 0.062 and 0.334 +/- 0.066 ng/ml on the day of oestrus in buffalo-heifers and buffalo-cows, respectively. The values were around 1 ng/ml till day 6, followed by a gradual increase to a peak average value of 4.888 +/- 0.399 and 5.119 +/- 0.415 ng/ml on day 15 of the cycle in heifers and cows, respectively. Thereafter, the progesterone concentration fell abruptly to a level similar to that at oestrus. The mean progesterone value a day before oestrus was 0.488 +/- 0.067 and 0.577 +/- 0.053 ng/ml in buffalo-heifers and buffalo-cows, respectively. The mean progesterone concentration of different days of the cycle (except day 16) did not differ significantly (P / -0.01) between heifers and cows.     

The connection between GRKs and various signaling pathways involved in diabetic nephropathy

Diabetic nephropathy (DN) is a known microvascular complication in patients with diabetes mellitus. DN has become one of the main causes of death in diabetic patients. The occurrence and development of DN results from the comprehensive action of multi-factors, though the exact mechanism is not very clear. Recently, a study found that numerous pathways are activated during the course of the disease, including the PGE2-EP-G protein system, the renin-angiotensin system, protein kinase C, MAPK and oxidative stress, and transforming growth factor-β. G protein-coupled receptor kinases (GRKs), specifically recognize and phosphorylate agonist-activated G protein-coupled receptors, which play a major role in the above-mentioned pathways. The purpose of this paper is to review current information concerning the connection between GRKs and various signaling pathways involved in DN.     

Serum cation profile of broilers at various stages of exposure to deoxynivalenol

The present experiment was carried out to investigate if levels of serum cations in broilers are modulated differently at various stages of exposure to deoxynivalenol (DON). Male broiler chicks at 7 days of age were fed a basal diet (0.27 mg of DON; 0.01 mg of zearalenone/kg), or either a low DON diet (1.68 mg of DON; 0.15 mg of zearalenone/kg) or a high DON diet (12.21 mg of DON; 1.09 mg of zearalenone/kg) produced using extracts from Fusarium graminearum cultures. Blood samples from the birds were collected during weeks 2, 4, and 5 of exposure. The high DON diet resulted in lower serum calcium levels compared to the basal diet at all the 3 sampling stages, while the low DON diet resulted in lower serum calcium levels only during weeks 2 and 5. Serum potassium levels were reduced under both the DON diets during weeks 2 and 5, while no diet-associated changes were found for serum levels of magnesium, sodium, and zinc. Under the present experimental conditions, the serum levels of calcium were consistently modulated in the broilers exposed to the DON-contaminated diets. The modulation of serum levels of potassium was, however, dependent upon the stage of exposure to DON.     

Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

雌性中缅树鼩繁殖期尿液的挥发性成分分析

正动物化学通讯包含信号发出者、化学信号、信号接收者三要素。尿液、粪便及特化腺分泌物是哺乳动物的主要气味源,由醇、烷烃、酸、酯、肽、蛋白质等组成,且其化学成分较为复杂(Novotny et al.,1999;Zhao and Wang,2010;Zhang and Zhang,2011)。尿液中化学信号发挥着极为重要作用,可以编码多种信息,如编码身体质量     

Glycation in diabetic nephropathy

The kidney is an extremely complex organ with broad ranging functions in the body, including but not restricted to waste excretion, ion and water balance, maintenance of blood pressure, glucose homeostasis, generation of erythropoietin and activation of vitamin D. With diabetes, many of these integral processes are interrupted via a combination of haemodynamic and metabolic changes including increases in the accumulation of proteins modified by advanced glycation, known as advanced glycation end products (AGEs). Indeed, hyperglycaemia and the redox imbalances seen with diabetes are each independent accelerants for the production of AGEs, which synergistically combine in this disorder. In addition, as kidney function declines, characterised by a loss of glomerular filtration, the excretion of AGEs is decreased, possibly exacerbating renal injury by further elevating the body’s tissue and circulating AGE pool. Therefore, it has become apparent that decreasing the accumulation of AGEs or interrupting their downstream effects on the kidney, are desirable therapeutic targets for the treatment of diabetic renal disease.     

RAGE in diabetic nephropathy

As is diabetes itself, diabetic angiopathy is a multi-factorial disease. Advanced glycation endproducts (AGE) cause vascular cell derangement characteristic of diabetes, and this is mainly mediated by their interaction with receptor for AGE (RAGE). When made diabetic, RAGE-overexpressing transgenic mice exhibited exacerbation of the indices of nephropathy, and this was prevented by the inhibition of AGE formation. On the other hand, RAGE-deficient animals showed amelioration of diabetic nephropathy. Accordingly, AGE and RAGE should be regarded as environmental and cellular accounts and as a potential therapeutic target for diabetic nephropathy. In effect, substances that inhibit the formation of AGE, break preformed AGE, change metabolic flows away from glycation, antagonize RAGE, and capture RAGE ligands have been proven as effective remedies against this life-threatening disease.     

Urinary and plasma proteomics to discover biomarkers for diagnosing between diabetic nephropathy and minimal change nephrotic syndrome or membranous nephropathy

The choice of treatment for primary nephrotic syndrome depends on the pathologic type of the disorder. Renal biopsy is necessary for a definitive diagnosis, but it is burdensome for the patients, and can be avoided if tests could be performed using urine or plasma. In this study, we analyzed 100 urinary proteins, 141 plasma proteins, and 57 urine/plasma ratios in cases of diabetic nephropathy (DN; n = 11), minimal change nephrotic syndrome (MCNS; n = 14), and membranous nephropathy (MN; n = 23). We found that the combination of urinary retinol-binding protein 4 and SH3 domain-binding glutamic acid-rich-like protein 3 could distinguish between MCNS and DN, with an area under the curve (AUC) of 0.9740. On the other hand, a selectivity index (SI) based on serotransferrin and immunoglobulin G, which is often used in clinical practice, distinguished them with an AUC of 0.9091. Similarly, the combination of urinary afamin and complement C3 urine/plasma ratio could distinguish between MN and DN with an AUC of 0.9842, while SI distinguished them with an AUC of 0.8538. Evidently, the candidates identified in this study were superior to the SI method. Thus, the aim was to test these biomarkers for accurate diagnosis and to greatly reduce the burden on patients.     

Notch signaling in diabetic nephropathy

Notch signaling is an evolutionarily conserved cell-cell signaling system that controls the fate of cells during development. In this review, we will summarize the literature that notch signaling during development controls nephron number and segmentation and therefore could influence kidney disease susceptibility. We will also review the evidence that Notch is reactivated in adult-onset diabetic kidney disease where it promotes the development of nephropathy including glomerulopathy, tubulointerstitial fibrosis and possibly arteriopathy and inflammation. Finally, we will review the evidence that blockade of pathogenic Notch signaling alters the natural history of diabetic nephropathy and thus could represent a novel therapeutic approach to the management of diabetic kidney disease.     

Prognosis in diabetic nephropathy.

OBJECTIVE--To assess the effect of long term antihypertensive treatment on prognosis in diabetic nephropathy. DESIGN--Prospective study of all insulin dependent diabetic patients aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Memorial Hospital. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--Forty five patients (20 women) with a mean age of 30 (SD 7) years and a mean duration of diabetes of 18 (7) years at onset of persistent proteinuria were followed until death or for at least 10 years. INTERVENTIONS--Antihypertensive treatment was started a median of three (0-13) years after onset of nephropathy. Four patients (9%) received no treatment, and 9 (20%), 13 (29%), and 19 (42%) were treated with one, two, or three drugs, respectively. The median follow up was 12 (4-15) years. MAIN OUTCOME MEASURES--Arterial blood pressure and death. RESULTS--Mean blood pressure at start of antihypertensive treatment was 148/95 (15/50) mm Hg. Systolic blood pressure remained almost unchanged (slope -0.01 (95% confidence interval -0.39 to 0.37) mm Hg a year) while diastolic blood pressure decreased significantly (0.87 (0.65 to 1.10) mm Hg a year) during antihypertensive treatment. The cumulative death rate was 18% (8 to 32%) 10 years after onset of nephropathy, in contrast to previous reports of 50% to 77% 10 years after onset of nephropathy. As in previous studies, uraemia was the main cause of death (9 patients; 64%). CONCLUSIONS--The prognosis of diabetic nephropathy has improved during the past decade largely because of effective antihypertensive treatment.     

糖尿病肾病遗传学研究进展

糖尿病肾病是糖尿病最严重的慢性并发症之一, 不同种族的发病率分析和家族聚集性研究显示遗传因素是糖尿病肾病发生、发展的重要因素。文章从3个方面对糖尿病肾病的遗传学研究进展进行综述：“候选基因”的关联研究、连锁分析和全基因组关联研究。关联研究及荟萃分析显示一些候选基因与糖尿病肾病显著相关, 包括ACE、AGT和PPARG等基因; 连锁分析及全基因组连锁分析发现多个糖尿病肾病的易感染色体位点; 随着高通量测序技术和芯片技术的发展, 全基因组关联研究已成为糖尿病肾病遗传学研究的重要途径。虽然遗传因素在糖尿病肾病发病中占据重要的位置, 但还不能完全解释糖尿病肾病的发病原因, 因为糖尿病肾病的发生还受环境因素的影响, 然而糖尿病肾病的遗传学研究可为糖尿病肾病发病机制研究以及药物治疗靶点研究提供一定的理论依据。     

Polyadenylated mRNAs from various developmental stages of Xenopus laevis. Role of 26 S mRNA

In Xenopus laevis embryos, the 26 S polyadenylated mRNA, coding for the myosin heavy chain, shows a maximum relative concentration as measured by the 3H-poly(U)-hybridization technique, at the neural-plate stage (st. 12.5 of Nieuwkoop and Faber, [NF]) only in the dorsal (ectodermal and mesodermal) region, i.e. shortly before the morphological appearance of the somites. On the contrary, myosin-heavy-chain mRNA cannot be observed in the ventral region with the same technique. This 26 S mRNA begins to be hybridizable at the gastrula stage (st. 10 NF). Polyadenylated mRNAs from postgastrula stages were translated in a cell-free system of rabbit reticulocytes, and the translation products were analyzed by polyacrylamide-gel electrophoresis and immunoprecipitation. It was found that protein recognizable as the heavy chain of the muscle myosin had been translated. Its possible role on the induction of somites is discussed.     

3,5-Diiodo-l-thyronine ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats

3, 5-Diiodothyronine (T2), a natural metabolite of triiodothyronine (T3) from deiodination pathway, can mimic biologic effects of T3 without inducing thyrotoxic effects. Recent studies revealed T3 acted as a protective factor against diabetic nephropathy (DN). Nevertheless, little is known about the effect of T2 on DN. This study was designed to investigate whether and how T2 affects experimental models of DN in vivo and in vitro. Administration of T2 was found to prevent significant decrease in SIRT1 protein expression and activity as well as increases in blood glucose, urine albumin excretion, matrix expansion, transforming growth factor-β1 expression, fibronectin and type IV collagen deposition in the diabetic kidney. Concordantly, similar effects of T2 were exhibited in the cultured rat mesangial cells (RMC) exposed to high glucose and that could be abolished by a known SIRT1 inhibitor, sirtinol. Moreover, enhanced NF-κB acetylation and JNK phosphorylation present in both diabetic rats and high glucose-treated RMC were distinctly dampened by T2. Collectively, these results suggested that T2 was a protective agent against renal damage in diabetic nephropathy, whose action involved regulation of SIRT1.     

Comparative analysis of diabetic nephropathy and non-diabetic nephropathy disease

ObjectiveClinical symptoms of diabetic nephropathy patients and non-diabetic nephropathy are compared and analyzed, hemodialysis effect and quality of life of two kinds of nephrotic patients are analyzed.MethodsRespectively extract 1300 cases of diabetic nephropathy and non-diabetic nephropathy patients admitted to different hospitals during December 2011-December 2014. Based on whether the patient suffers from diabetes, they were divided into diabetic group and control group. Hemodialysis of two groups of patients were followed up to observe effectiveness of blood treatment, and complications were observed after one year of follow-up.ResultsHematodialysis effectiveness of diabetic nephropathy patients is significantly lower than that of non-diabetic nephropathy group. After 1 year’s follow-up, it can be found that survival rate of diabetic nephropathy patients is much lower than that of control group. In statistical comparison of data involved in the two groups of patients, P < 0.05, the difference is statistically significant.ConclusionTreatment effect of diabetic nephropathy patients is relatively poor compared to that of non-diabetic patients. In clinics, management and prevention of diabetic patients should be strengthened to avoid complication of nephropathy which brings serious injury to patients.