Nephroprotective Effect of Leu-Ile-Lys Tripeptide in Experimental Diabetes Mellitus

Bulletin of Experimental Biology and Medicine - We studied the effect of tripeptide Leu-Ile-Lys on kidney function in rats with experimental diabetes mellitus modeled by single intraperitoneal...     

Tissue Distribution of T-Lymphocytes and Ia-Expressing Cells in Rat Kidney Grafts

In a rat kidney transplantation model, DA kidneys were transplanted into Lewis rats. Syngeneic Lewis transplantations were studied as controls. Histologic evaluation was made, and immunohistochemical staining with a single-staining peroxidase-antiperoxidase technique on frozen sections was performed after 2, 4, 6, and 8 days. Antibodies for Ia antigen (Ox 6), 'suppressor/cytotoxic' cells (Ox 8), pan-T cells (W 3/13), and 'helper/inducer' cells (W 3/25) were used. Allogeneic grafts were almost completely rejected in 8 days. Syngeneic grafts also showed lymphocyte infiltrates, somewhat later than allogeneic ones, but were not rejected. In these infiltrates W 3/25-positive cells dominated, being even more numerous than W 3/13-positive cells. Relatively fewer Ox 8-positive cells were seen in the infiltrates of syngeneic than in allogeneic transplants. Infiltrates occurred later in the renal medulla than in the cortex. Perivascular infiltrates with cells of all investigated phenotypes were seen earlier in allogeneic grafts than in syngeneic ones. All tubular cells within one renal tubule appeared either Ox 6-positive or -negative. With time, all tubules in the allogeneic transplants became Ox 6-positive. Some increase of Ox 6-positive tubules was also seen in syngeneic transplants.     

Dapagliflozin Ameliorates Lipopolysaccharide Related Acute Kidney Injury in Mice with Streptozotocin-induced Diabetes Mellitus

Sepsis, which is a serious medical condition induced by infection, has been the most common cause of acute kidney injury (AKI) and is associated with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral antidiabetic drug that has greatly improved the cardiovascular and renal outcomes in patients with type 2 diabetes independent of its sugar lowering effect, possibly by attenuation of the inflammatory process. We investigated the effect of the SGLT2 inhibitor dapagliflozin on lipopolysaccharide (LPS)-induced endotoxic shock with AKI in streptozotocin-induced diabetic mice. Endotoxin shock with AKI was induced by intravenous injection of 10 mg/kg LPS in C57BL6 mice with streptozotocin-induced diabetic mellitus with or without dapagliflozin treatment. Observation was done for 48 hours thereafter. In addition, NRK-52E cells incubated with LPS or dapagliflozin were evaluated for the possible mechanism. Treatment with dapagliflozin attenuated LPS-induced endotoxic shock associated AKI and decreased the inflammatory cytokines in diabetic mice. In the in vitro study, dapagliflozin decreased the expression of inflammatory cytokines and reactive oxygen species and increased the expressions of AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor, and heme oxygenase 1. These results demonstrated that dapagliflozin can attenuate LPS-induced endotoxic shock associated with AKI; this was possibly mediated by activation of the AMPK pathway.     

Initial Stages of the Insulin Signaling System in the Brain of Rats with Experimental Diabetes Mellitus

We studied reactivity of insulin signal pathway elements, insulin receptor and insulin receptor substrate protein-2 (IRS2 protein), in rat brain in response to insulin insufficiency and insulin resistance during the development of experimental type 1 or type 2 diabetes mellitus. In type 1 diabetes mellitus characterized by acute insulin insufficiency, specific binding of insulin in rat brain increased 2-fold in comparison with the control and IRS2-gene expression in rat hypothalamus and cortex 2-4 fold surpassed the normal values. In type 2 diabetes mellitus (110 and 190 days of development), changes in the test parameters in rat brain were less pronounced. These findings attest to involvement of the brain insulin signal pathway into the response to systemic insulin deficiency in type 1 diabetes mellitus.     

2型糖尿病合并颈动脉粥样硬化患者外周血单个核细胞凋亡相关斑点样蛋白mRNA的表达

目的:分析2型糖尿病(T2DM)合并颈动脉粥样硬化(CAS)患者外周血单个核细胞(PBMCs)中衔接蛋白凋亡相关斑点样蛋白(ASC)mRNA的表达及作用。方法:根据华盛顿大学CAS斑块超声分级标准将107例T2DM患者分为单纯T2DM组(n=26)、T2DM轻度斑块组(n=32)、T2DM中度斑块组(n=38)和T2DM重度斑块组(n=11)。另选非T2DM的CAS患者作为单纯CAS组(n=35),以及体检健康者作为正常对照组(n=35)。采用实时荧光定量聚合酶链反应(RT-FQ-PCR)技术检测各组PBMCs中ASC mRNA表达水平。统计分析各组差异及ASC mRNA水平与CAS斑块严重程度的关系。结果:各病例组ASC mRNA表达水平显著高于正常对照组(P0.05),T2DM合并CAS组ASC mRNA表达水平显著高于单纯CAS组(P0.01);ASC mRNA表达水平轻度斑块组中度斑块组重度斑块组,即ASC mRNA表达水平与T2DM患者CAS斑块程度呈明显负相关(r=-0.43,P0.05)。结论:ASC mRNA表达增加可能是T2DM合并AS的发病因素和CAS斑块活跃性的指征。     

The Dysfunction of NK Cells in Patients with Type 2 Diabetes and Colon Cancer

Glucose metabolism disorders influence anticarcinogenic function of natural killer (NK) cells. The aim of this study was to evaluate the number and cytotoxic activity of NK cells in type 2 diabetic (T2D) patients with negative family history of cancer, type 2 diabetic subjects with newly diagnosed untreated colon cancer (T2DCC) and patients without type 2 diabetes with newly diagnosed, untreated colon cancer (CC). Incubation tests were performed in 18 T2D patients, treated with diet and oral antidiabetic agents, 16 T2DCC; cT1-4N0M0 (c-clinical diagnosis based on computed tomography, colonoscopy and histopathology) treated with diet and oral antidiabetic agents and 16 normoglycemic CC; cT1-4N0M0. Control group included 18 metabolically healthy (with normal fasting glucose and normal glucose tolerance) subjects (HS) with negative family history of cancer, matched by age, BMI and waist circumference. Peripheral blood mononuclear cells were isolated by means of gradient centrifugation. The K562 human erythroleukemia cell line served as the standard target for human NK cytotoxicity assay. The T2D revealed an increased number of NK cells (13.56 ± 5.9 vs 9.50 ± 4.8 %; p < 0.05) when compared with HS, yet these cells had a decreased activity (3.3 ± 2.5 vs 9.4 ± 3.6 %; p < 0.01). The CC demonstrated a decreased activity (2.9 ± 1.8 %; p < 0.01) but a similar number (8.82 ± 3.7 %; not significant) of NK cells when compared to HS. The T2DCC NK cells were characterized by trace cytotoxic activity (1.1 ± 0.7 %; p < 0.01) and nearly three times greater amount (21.24 ± 7.5 %; p < 0.01) when compared to T2D. Type 2 diabetes and CC are associated with disadvantageous alterations of NK cells, leading to impairment in their cytotoxic activity. The impaired activity of NK cells in T2D can be involved in the increased carcinogenic risk and can promote a higher incidence of CC.     

Mechanisms of Therapeutic Effects of Granulocytic Colony-Stimulating Factor in Experimental Diabetes Mellitus

We studied the mechanisms of therapeutic effects of granulocytic colony-stimulating factor in experimental diabetes mellitus. It was found that this preparation increased the number of mesenchymal precursor cells in the bone marrow and peripheral blood with subsequent increase in the content of progenitor cells in the pancreas. These results attest to mobilization of mesenchymal progenitor cells and their migration into the damaged tissue accompanied by morphofunctional recovery of the insulin-producing apparatus. Translated from Kletochnye Tehnologii v Biologii i Medicine, No. 4, pp. 230–233, November, 2008     

妊娠糖尿病患者血脂检验在临床诊断中的应用分析

目的 研究妊娠糖尿病孕妇血脂检验在临床诊断中的应用效果。方法 选择2016年1月~12月收治的50例妊娠糖尿病孕妇,纳入干预组,同时选择同时段来我院体检的健康孕妇50名,纳入常规组,评价两组孕妇血脂监测结果及不同年龄段孕妇血脂水平。结果 干预组孕妇低密度脂蛋白、三酰甘油、总胆固醇等血脂水平均高于常规组,高密度脂蛋白值低于常规组,差异有统计学意义（P＜0.05）。不同年龄段的孕妇血脂各指标水平结果不同,LDL-C、TG、TC等水平随着孕妇年龄增大而增加,而HDL-C水平则因孕妇年龄增大而减少。结论 妊娠糖尿病患者体内血脂水平均异常,且血脂水平与孕妇年龄存在一定联系。     

糖尿病并脑梗塞与糖基化血红蛋白关系的探讨

糖尿病是导致脑梗塞发生的主要危险因素之一，能增加脑梗塞的发病率．对我院30例糖尿病合并脑梗塞的病例进行分析，发现该组病人精基化血红蛋白的水平明显高于糖尿病对照组，P＜0．001，有显著性差异，提示糖尿病合并脑梗塞的发病可能和蛋白非酶糖化有关．因此，要预防脑梗塞的发生，关键在于控制好血糖．减少蛋白非酶糖化，尽可能将糖基化血红蛋白控制于理想水平．     

利拉鲁肽对首诊2型糖尿病患者血糖、血脂及T细胞亚群的影响

目的 探讨利拉鲁肽治疗首诊超重或肥胖2型糖尿病患者的效果及其对T细胞亚群的影响。方法 选取2018年2月~2019年6月我院收治的72例确诊为2型糖尿病超重或肥胖患者,采用随机数字表法分为对照组和研究组,每组36例。对照组予以常规治疗,研究组在对照组基础上加用利拉鲁肽治疗,比较两组治疗前后血糖水平（FPG、BPG、HbA1c）、空腹胰岛素+C肽、餐后2h胰岛素+C肽水平、BMI、血脂（HDL-C、LDL-C、VLDL-C、TC、TG）以及CD4+、CD4+/CD8+水平。结果 治疗后,研究组FPG、BPG、HBA1c水平低于对照组（P＜0.05）,空腹胰岛素、餐后2h胰岛素和空腹C肽、餐后2h C肽水平高于对照组（P＜0.05）;研究组BMI水平低于对照组（P＜0.05）;研究组TG、TC、LDL-C、VLDL-C水平低于对照组,HDL-C水平高于对照组（P＜0.05）;研究组CD4+、CD4+/CD8+高于对照组（P＜0.05）。结论 利拉鲁肽可调节CD4+T细胞亚群平衡,改善胰岛素β细胞功能并降低胰岛素抵抗,可更好控制2型糖尿病患者血糖水平,改善血脂水平,降低体质量。