实验性糖尿病大鼠肝,肾,心,脑脂肪酸代谢的动态变化

报道对链脲佐菌素（STZ）诱导的实验性糖尿病大鼠几种重要脏器（肝、肾、心、脑）卵磷脂、脑磷脂中脂肪酸构成的变化。不饱和脂肪酸变化的模式（C18：2n-6，C20：3n-6，C22：5n-3，C22：6n-3增加，C20：4n-6降低）基本相同，改变的先后顺序是肝→心、肾→脑。     

两种糖尿病肾病大鼠模型的比较

目的 :比较两种糖尿病肾病大鼠模型的优劣。方法 :采用单侧肾切除合并尾静脉注射链尿佐菌素(Streptozotocin ,STZ) (STZ加单侧肾切除组 )及单纯腹腔注射链尿佐菌素 (STZ) (STZ组 )两种方法 ,分别将Wister大鼠造成糖尿病肾病大鼠模型 ,然后检测二种方法在空腹血糖 ,尿 β2 -微球蛋白 (β2 -microglobulin ,β2 -MG)及尿微量白蛋白 (albulin ,Alb)的排出量方面的差异。结果 :STZ组空腹血糖 (33 5 9mmol/L)明显高于STZ加单侧肾切除组 (16 12mmol/L) ;STZ +单侧肾切除组β2 -微球蛋白 ,尿微量白蛋白的排出量较STZ组有明显增加 ,其病理改变也较明显。结论 :STZ合并单侧肾切除更符合糖尿病肾病的病理改变。     

糖尿病引发股骨头缺血性坏死骨代谢的变化

目的:通过观察糖尿病引发股骨头缺血性坏死大鼠的骨代谢变化特征,分析其在糖尿病性股骨头缺血坏死发病过程中的作用.方法:采用腹腔内1次注射60mg/kg体重链脲佐菌素(STZ)的方法,建立速发型STZ-DM模型,进行相关骨代谢指标的测定.结果:实验组大鼠股骨头软骨下骨小梁稀疏、断裂,空缺骨陷窝显著增多;股骨头压缩强度明显降低;骨Ca、HOP含量及Ca/HOP比值均有显著降低;血清BGP、血Ca及钙磷乘积显著下降;尿Ca、P、HOP排泄量均有显著增多;结论:糖尿病存在骨代谢紊乱,引发骨质疏松,股骨头因应力作用引起软骨下骨压缩塌陷,压迫骨内微血管而继发缺血坏死.     

通络益肾汤对链脲佐菌素DN大鼠疗效的实验研究

目的 观察通络益肾汤对链脲佐菌素（STZ）糖尿病肾病大鼠的疗效。方法采用STZ糖尿病肾病大鼠模型，分为正常组、病理组、通络益肾汤治疗组、西药治疗组（糖适平＋洛汀新）。观察各组大鼠治疗前后的一般状况、血糖、肾功（BUN、Scr）、肾脏病理等指标的变化。结果与病理组比较，通络益肾汤治疗组大鼠一般状况改善较好，血糖明显下降（P＜0．05），血清BUN、Scr显著降低（P＜0．01）。通络益肾汤治疗组与西药组比较，各项指标无明显差异。结论通络益肾汤能延缓糖尿病肾病的病理进展，对糖尿病肾病有确切的治疗效果。     

Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats

We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37–45 weeks after the treatment with STZ (50 or 75 mg/kg, i.v.) and NA (350 mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules.     

Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats

The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ⁹-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ⁹-THC treated, (3) diabetic, and (4) diabetic + Δ⁹-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ⁹-THC and Δ⁹-THC treated diabetic groups received 3 mg/kg/day of Δ⁹-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin–biotin–peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic + Δ⁹-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic + Δ⁹-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes + Δ⁹-THC group showed a decrease compared to the diabetic group. These results indicate that Δ⁹-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.     

Altered platelet calsequestrin abundance,Na/Ca exchange and Ca signaling responses with the progression of diabetes mellitus

Introduction

Downregulation of calsequestrin (CSQ), a major Ca^2 + storage protein, may contribute significantly to the hyperactivity of internal Ca^2 + ([Ca^2 +]_i) in diabetic platelets. Here, we investigated changes in CSQ-1 abundance, Ca^2 + signaling and aggregation responses to stimulation with the progression of diabetes, especially the mechanism(s) underlying the exaggerated Ca^2 + influx in diabetic platelets.

Materials and methods

Type 1 diabetes was induced by streptozotocin in rats. Platelet [Ca^2 +]_i and aggregation responses upon ADP stimulation were assessed by fluorescence spectrophotometry and aggregometry, respectively. CSQ-1 expression was evaluated using western blotting.

Results

During the 12-week course of diabetes, the abundance of CSQ-1, basal [Ca^2 +]_i and ADP-induced Ca^2 + release were progressively altered in diabetic platelets, while the elevated Ca^2 + influx and platelet aggregation were not correlated with diabetes development. 2-Aminoethoxydiphenyl borate, the store-operated Ca^2 + channel blocker, almost completely abolished ADP-induced Ca^2 + influx in normal and diabetic platelets, whereas nifedipine, an inhibitor of the nicotinic acid adenine dinucleotide phosphate receptor, showed no effect. Additionally, inhibition of Na⁺/Ca^2 + exchange induced much slower Ca^2 + extrusion and more Ca^2 + influx in normal platelets than in diabetic platelets. Furthermore, under the condition of Ca^2 +-ATPase inhibition, ionomycin caused greater Ca^2 + mobilization and Ca^2 + influx in diabetic platelets than in normal platelets.

Conclusions

These data demonstrate that platelet hyperactivity in diabetes is caused by several integrated factors. Besides the downregulation of CSQ-1 that mainly disrupts basal Ca^2 + homeostasis, insufficient Na⁺/Ca^2 + exchange also contributes, at least in part, to the hyperactive Ca^2 + response to stimulation in diabetic platelets.     

IL-33 receptor ST2 deficiency attenuates renal ischaemia–reperfusion injury in euglycaemic,but not streptozotocin-induced hyperglycaemic mice

Aim

Kidney hypoxia can predispose to the development of acute and chronic renal failure in diabetes. Ischaemia–reperfusion injury (IRI) causes inflammation, and diabetes is known to exacerbate this inflammatory response in the kidney, whereas alarmin IL-33 could act as an innate immune mediator during kidney IRI. Thus, the present study examined the impact of genetic IL-33 receptor ST2 deficiency (ST2?/?) on renal IRI in euglycaemic and hyperglycaemic mice.

Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients

Type 1 Diabetes Mellitus (T1D) results from the destruction of insulin-producing beta cells in the pancreas by autoreactive T cells. Myeloid derived suppressor cells (MDSCs) are a recently identified immune cell subset that down-regulate T cells. Whether defects in MDSC numbers or function may contribute to T1D pathogenesis is not known. We report here that MDSCs are unexpectedly enriched in peripheral blood of both mice and patients with autoimmune diabetes. Peripheral blood MDSCs from T1D patients suppressed T cell proliferation in a contact-dependent manner; however, suppressive function could be enhanced with in vitro cytokine induction. These findings suggest that native T1D MDSCs are not maximally suppressive and that strategies to promote MDSC suppressive function may be effective in preventing or treating T1D.