Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes

Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized.     

Design,synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1

Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK‐875, AMG‐837, and LY2881835. Among them, most promising compounds 7 , 14 , and 15 were obtained with EC₅₀ values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK‐875 (95.1 nM). During Oral glucose tolerance test in normal mice, compound 7 , 14 , and 15 had significant glucose‐lowering effect at the dose of 50 mg/kg. Furthermore, compound 15 (50 mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold.     

Heterogeneity of human serum high-density lipoprotein (HDL 2 )

A technique is described for the detection of free fatty acids, triglycerides, wax esters and cholesterol esters on thin-layer Chromatographic plates. The fatty acids present in each fraction can be recovered from the plates after detection and quantitatively measured by gas-liquid chiomatography. This procedure has been sucessfully applied to the analysis of skin surface lipids.     

RA患者血清FFA、hs-CRP及TNF-α的水平变化与胰岛素抵抗的关系

目的：研究类风湿性关节炎（RA）患者血清游离脂肪酸（FFA）、高敏C-反应蛋白（hs-CRP）和肿瘤坏死因子（TNF-α）水平的变化及其与胰岛素抵抗的关系。方法：测定92例RA患者（稳定期53例,活动期39例）及50例正常人血清FFA、空腹胰岛素（fINS）、空腹血糖（fPS）,同时检测hs-CRP、TNF-α、血脂等指标,并计算胰岛素敏感指数（ISI）、稳态模型胰岛素抵抗指数（Homa-IR）,分析FFA水平的变化与胰岛素抵抗的关系。结果：非活动期和活动期RA患者,FFA、hs-CRP、TNF-α、Homa-IR、TG和LP（α）水平均较正常对照组显著升高（P〈0.05或P〈0.01）,且活动期RA组FFA、hs-CRP、TNF-α、fINS、Homa-IR、TG和LP（α）水平较非活动期RA患者明显升高（P〈0.05或P〈0.01）;直线相关分析显示,血清FFA水平与hs-CRP、TNF-α、fINS、Homa-IR、TG和LP（α）呈正相关（P〈0.01）,与ISI呈负相关（P〈0.01）。结论：RA患者血清FFA水平明显升高,且与hs-CRP、TNF-α及胰岛素抵抗密切相关。     

超氧化物歧化酶及游离脂肪酸检测在胰岛素抵抗疾病中的应用

目的 探讨超氧化物歧化酶(SOD)及游离脂肪酸(FFA)检测在胰岛素抵抗疾病中的应用价值.方法 选择300例2型糖尿病(DM2)患者,其中150例合并非酒精性脂肪肝(NAFLD),空腹采血检测超氧化物歧化酶(SOD)、游离脂肪酸(FFA)、胰岛素(INS)、葡萄糖(FPG)、脂类等实验室指标,同时做肝脏瞬时弹性检查(FibroScan)和受控衰减参数(CAP);选择150例体检健康者为对照组,做相同检测.结果 糖尿病组和合并NAFLD组检测结果进行对比,各项指标的差异均具有统计学意义(P＜0.05),糖尿病组、合并NAFLD组与对照组的检测结果进行对比,各项指标的差异均具有统计学意义(P＜0.05).结论 超氧化物歧化酶及游离脂肪酸检测在胰岛素抵抗疾病中有重要的应用价值.     

Liver mitochondrial function and redox status in an experimental model of non-alcoholic fatty liver disease induced by monosodium L-glutamate in rats

The purpose of this work was to determine if mitochondrial dysfunction is involved in the development of non-alcoholic fatty liver disease (NAFLD). Using a model of obesity induced by the neonatal treatment of rats with monosodium l-glutamate (MSG), several parameters of liver mitochondrial function and their impact on liver redox status were evaluated. Specifically, fatty acid β-oxidation, oxidative phosphorylation and Ca²⁺-induced mitochondrial permeability transition were assessed in isolated liver mitochondria, and reduced glutathione (GSH), linked thiol contents and the activities of several enzymes involved in the control of redox status were measured in the liver homogenate. Our results demonstrate that liver mitochondria from MSG-obese rats exhibit a higher β-oxidation capacity and an increased capacity for oxidising succinate, without loss in the efficiency of oxidative phosphorylation. Also, liver mitochondria from obese rats were less susceptible to the permeability transition pore (PTP) opening induced by 1.0 μM CaCl₂. Cellular levels of GSH were unaffected in the livers from the MSG-obese rats, whereas reduced linked thiol contents were increased. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione peroxidase were increased, while catalase activity was unaffected and superoxide dismutase activity was reduced in the livers from the MSG-obese rats. In this model of obesity, liver fat accumulation is not a consequence of mitochondrial dysfunction. The enhanced glucose-6-phosphate dehydrogenase activity observed in the livers of MSG-obese rats could be associated with liver fat accumulation and likely plays a central role in the mitochondrial defence against oxidative stress.     

Effect of insulin on glucagon enhanced lipolysis in vitro

Summary Glucagon in concentrations similar to those found in human plasma markedly stimulates lipolysis in rat adipose tissuein vitro. The effects of these physiological concentrations of glucagon are reduced or abolished by insulin at concentrations of 25 and 100U/ml. Considering the marked insulinogenic effect of glucagon these observations may provide an explanation for the delayed increase of blood FFA observed after glucagon injectionin vivo.This work was supported by the Fonds National de la Recherche Scientifique and the Fonds de la Recherche Scientifique Médicale, Belgium.     

老年2型糖尿病合并血管并发症患者C反应蛋白与游离脂肪酸水平分析

 目的 研究老年2型糖尿病及合并血管并发症患者C反应蛋白(CRP)和游离脂肪酸(FFA)的变化及相关性,探讨C反应蛋白和游离脂肪酸在老年糖尿病合并血管并发症发生中的作用.方法 检测2型糖尿病伴血管并发症组102例,无血管并发症组142例,正常对照组62例血清C反应蛋白与游离脂肪酸水平,分析其差异与相关性.结果 伴血管并发症组和无血管并发症组的血清CRP、FFA与正常对照组比较均差异显著(P＜0.05).伴血管并发症组CRP与FFA呈正相关,相关系数r=0.582(P＜0.05); FFA和CRP基本无关,相关系数分别为r=0.126和r=0.198(P>0.05).结论 老年2型糖尿病伴血管并发症患者血清中CRP和FFA浓度升高,且高于无血管并发症患者,CRP与FFA水平更具有一致性,血清CRP与FFA检查可用于监测老年2型糖尿病有无血管并发症.     

Growth hormone secretion in diabetic retinopathy

Summary The plasma HGH response to insulin-induced hypoglycemia (0.2 U/kg) and the 24-h plasma HGH pattern during a normal day have been studied in 14 non obese long-term insulin-dependent diabetics with proliferative retinopathy, mean age 39 ± 2 (ranging between 24 and 50 years). Plasma glucose and FFA were also determined. The results were compared with those of 18 normal subjects of similar age and weight. The mean plasma HGH response to insulin in retinopathic diabetics was slightly lower (with no significant differences) than in controls in whom hypoglycemia was induced with a smaller dose of insulin (0.1 U/kg). This pattern of plasma HGH could be related to the delayed plasma glucose fall observed in retinopathic diabetics in comparison to normal subjects, even if the HGH peak after insulin in both groups (18.61 ± 4.32 ng/ml in retinopathic diabetics, 27.43 ± 4.19 in controls) did not seem to be correlated to the degree of hypoglycemia, but rather to the age of the subjects. Plasma HGH pattern, studied with blood samples taken every three hrs during a normal day, did not reveal differences between the diabetics and controls. Plasma glucose, however, was higher in retinopathic diabetics than in controls in spite of the insulin treatment. These results show that in diabetic patients with retinopathy, increased HGH secretion does not occur in conditions of ordinary life or after insulin-induced hypoglycemia, although the HGH plasma levels observed in retinopathic diabetics could be considered too high in relation to the elevated blood glucose levels. Traduzione a cura degli AA.