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.     

Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats

Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (P<0.05). Additionally, peripheral blood mononuclear cells isolated from glycine-treated diabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (P<0.05). Glycine-treated rats had a less intense corporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.     

Acarbose treatment and diabetic nephropathy in the Cohen diabetic rat

Groups of Cohen diabetic rats, aged 30 days were treated with Acarbose (40 mg per 100 g sucrose diet) for 3, 5 and 7 months. Siblings of the same sex were used as controls and fed the sucrose diet alone. The dose of Acarbose was adjusted in a preliminary study and found to be tolerated by the animals. Acarbose treatment resulted in a significant reduction of the 2 hr postprandial blood glucose. No elevation of the plasma insulin was noted. A significant decreased incidence and severity of glomerulosclerosis was not in the 3 months Acarbose treated groups (P less than 0.05) and in the 5 and 7 months (P less than 0.01) in comparison with the controls. In the 7 months Acarbose treated group the longevity was significantly longer than in the control (P less than 0.05). In the 3 and 5 months groups, increased longevity was not apparent as the animals were sacrificed before having the opportunity to manifest the difference.     

Understanding diabetic retinopathy

<正>A recent survey shows that diabetes affect 92.4 million people in mainland China[1],among which 16.9 million have diabetic retinopathy(DR)[2].DR is one of the major causes of blindness in the working age population in both     

糖尿病及糖尿病心血管并发症患者肠道菌群的特征

【目的】比较2型糖尿病患者、糖尿病心血管并发症患者与健康人肠道菌群差异,分析肠道菌群与血糖、血脂等临床指标的关联,探讨肠道细菌在2型糖尿病、糖尿病心血管并发症发生、发展中的作用。【方法】招募健康人251例、糖尿病心血管并发症患者160例及糖尿病患者295例,三组各随机选取30例、30例和40例,进行血液生化指标分析和肠道菌群的宏基因组检测。【结果】与健康对照组比较,糖尿病心血管并发症组和2型糖尿病组血清丙氨酸氨基转移酶、碱性磷酸酶、甘油三酯、空腹血糖、胰岛素、糖化血红蛋白指标显著升高(P0.05);糖尿病患者组、糖尿病心血管并发症患者组的肠道菌群α-多样性明显降低,菌群发生改变。健康对照组中大部分优势菌属来自拟杆菌门和厚壁菌门,而糖尿病心血管并发症患者组和糖尿病患者组中大部分优势菌属则来自拟杆菌门、变形菌门和放线菌门。与健康对照组相比,糖尿病心血管并发症患者组和糖尿病患者组中,厚壁菌门比例明显下降,放线菌门和变形菌门比例明显上升。种水平上,空腹血糖与黏膜乳杆菌(Lactobacillus mucosae)、大肠埃希氏菌(Escherichia coli)、脆弱拟杆菌(Bacteroides fragilis)呈正相关,与细枝真杆菌(Eubacterium ramulus)、Roseburia inulinivorans、Roseburia hominis、挑剔真杆菌(Eubacterium eligens)、伶俐瘤胃球菌(Ruminococcus callidus)呈负相关;低密度脂蛋白胆固醇与嵴链球菌(Streptococcus cristatus)呈正相关,与Lachnospiraceae bacterium_6_1_63FAA和淀粉乳杆菌(Lactobacillus amylovorus)呈负相关;总胆固醇与血链球菌(Streptococcus sanguinis)呈正相关。【结论】2型糖尿病和糖尿病心血管并发症患者存在明显的糖脂代谢异常和肠道菌群失调,肠道菌群紊乱可能在糖尿病发病、进展过程中发挥重要作用。     

Neuroprotective properties of aucubin in diabetic rats and diabetic encephalopathy rats

In this study, we determined the neuroprotective effect of aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60?mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10?mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65?days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of aucubin could be seen not only in the short term (15?days) but also in the long term (45?days), which was a highly encouraging finding. These data suggest that aucubin may be a potential neuroprotective agent.     

West Indian diabetic population of a large inner city diabetic clinic.

West Indians form a sizable minority of diabetics attending many inner city diabetic clinics. There are 554 diabetics of West Indian origin on our computer files--7% of the total recorded clinic population. Of these 554 patients (56% female, 44% male), 70% have been diagnosed within the past five years; and only 9% have had diabetes for over 10 years; in only five (1%) was diabetes diagnosed before the age of 20. Sixteen per cent were taking insulin, but only 4% of the total West Indian population were truly insulin dependent. Of 65 patients admitted in hyperglycaemic coma or precoma over the past three years, 10 were of West Indian origin; eight of these 10 had hyperosmolar coma compared with only six of the remaining 55. We conclude that diabetics of West Indian origin attending our clinic show differences in the distribution of age and duration of diabetes from the caucasian population. Most are non-insulin dependent, and the frequency of hyperosmolar coma is higher than that of ketoacidosis. Diabetics of West Indian origin may have a different pattern of disease from the rest of the clinic population.     

Angiotensin and diabetic retinopathy

Diabetic retinopathy develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. In diabetes, damage to the retina occurs in the vasculature, neurons and glia resulting in pathological angiogenesis, vascular leakage and a loss in retinal function. The renin-angiotensin system is a causative factor in diabetic microvascular complications inducing a variety of tissue responses including vasoconstriction, inflammation, oxidative stress, cell hypertrophy and proliferation, angiogenesis and fibrosis. All components of the renin-angiotensin system including the angiotensin type 1 and angiotensin type 2 receptors have been identified in the retina of humans and rodents. There is evidence from both clinical and experimental models of diabetic retinopathy and hypoxic-induced retinal angiogenesis that the renin-angiotensin system is up-regulated. In these situations, retinal dysfunction has been linked to angiotensin-mediated induction of growth factors including vascular endothelial growth factor, platelet-derived growth factor and connective tissue growth factor. Evidence to date indicates that blockade of the renin-angiotensin system can confer retinoprotection in experimental models of diabetic retinopathy and ischemic retinopathy. This review examines the role of the renin-angiotensin system in diabetic retinopathy and the potential of its blockade as a treatment strategy for this vision-threatening 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.     

Meningitis in diabetic patients

Community acquired bacterial (CBM) meningitis in diabetic patients was analyzed for risk factors and outcome in a cohort of 201 cases of meningitis within last 17 years: 15 patients with diabetes mellitus and meningitis were identified and compared for etiology and mortality as well as for neurologic sequellae with all CBM cases.     

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.