糖尿病大鼠心肌超微结构改变及过氧化物酶体增殖激活受体gamma配体对其作用的研究

目的：明确糖尿病大鼠心肌超微结构改变及过氧化物酶体增殖激活受体（PPAR）gamma配体（罗格列酮）对之的作用。方法：建立6周和10周糖尿病大鼠组，其中10周糖尿病大鼠的1组用PPARgamma配体治疗，各组左心室心肌制作透射电镜标本。结果：STZ诱导的糖尿病大鼠心肌细胞胞浆肌原纤维束减少并断裂、融合，肌原纤维束与线粒体结构排列紊乱，线粒体崩解，细胞核固缩，核仁消失。10周组糖尿病大鼠心肌超微结构破坏比6周组明显。与未治疗组比，罗格列酮治疗组心肌结构完整、清晰，基本和正常大鼠心肌超微结构相似。结论：高血糖引起心肌超微结构损伤明显，糖尿病病程越长病变越明显；PPARgamma配体具有心肌保护作用，而且不依赖于降血糖。     

Adipose tissue and ovarian aging: Potential mechanism and protective strategies

Ovarian aging occurs approximately 10 years prior to the natural age-associated functional decline of other organ systems. With the increase of life expectancy worldwide, ovarian aging has gradually become a key health problem among women. Therefore, understanding the causes and molecular mechanisms of ovarian aging is very essential for the inhibition of age-related diseases and the promotion of health and longevity in women. Recently, studies have revealed an association between adipose tissue (AT) and ovarian aging. Alterations in the function and quantity of AT have profound consequences on ovarian function because AT is central for follicular development, lipid metabolism, and hormonal regulation. Moreover, the interplay between AT and the ovary is bidirectional, with ovary-derived signals directly affecting AT biology. In this review, we summarize the current knowledge of the complex molecular mechanisms controlling the crosstalk between the AT and ovarian aging, and further discuss how therapeutic targeting of the AT can delay ovarian aging.     

噻唑烷二酮类对非酒精性脂肪性肝病的治疗作用及机制

近年来研究认为过氧化体增殖物激活受体-γ激动剂—噻唑烷二酮类(TZD)对于非酒精性脂肪性肝病的治疗有一定的帮助,其可降低肝脏、肌肉和脂肪组织的胰岛素抵抗,降低血浆游离脂肪酸,减少肝脏细胞的脂肪沉积,抑制炎症。本文就TZD的治疗效果及其作用机制加以综述。     

吡格列酮对糖尿病大鼠肾脏的保护作用及其机制探讨

目的观察吡格列酮对糖尿病大鼠肾脏的保护作用并探讨其机制。方法采用链脲佐菌素(STZ)诱导糖尿病模型。24只大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)、吡格列酮干预组(3mg·kg-1·d-1,DT组),每组8只。12周末,测定各组相关生化指标。运用比色法检测肾皮质中丙二醛(MDA)的含量、铜锌超氧化物歧化酶(Cu-ZnSOD)及过氧化氢酶(CAT)的活性。同时留取肾标本作电镜观察。结果与NC组相比,DM组和DT组血糖、胆固醇、甘油三酯、血清胰岛素、C肽、尿素氮、血肌酐、肾重/体重和24h尿蛋白定量差异有统计学意义。DM组与NC组比较,肾皮质Cu-ZnSOD、CAT活性明显降低(P<0.01),MDA含量明显增加(P<0.01)。DT组与DM组比较,血糖、胆固醇、甘油三酯、血清胰岛素、C肽、尿素氮、血肌酐差异无统计学意义(P>0.05),肾重/体重和24h尿蛋白定量明显降低(P<0.05);肾皮质CAT和Cu-ZnSOD活性增加(P<0.05),肾皮质MDA含量降低(P<0.05)。结论吡格列酮对糖尿病大鼠肾脏有保护作用且此作用不依赖其降糖、降脂机制,可能与吡格列酮的抗氧化机制有关。     

吡格列酮治疗2型糖尿病合并脂肪肝疗效观察

目的评价吡格列酮对2型糖尿病合并脂肪肝的治疗作用及安全性。方法选择2型糖尿病合并非酒精性脂肪肝（NASH）患者198例,分成吡格列酮治疗组和对照组。观察和比较2组患者脂肪肝的变化情况。结果经6个月的观察,治疗组在改善脂肪肝程度、降低空腹胰岛素及改善肝功能等方面明显优于对照组。治疗组显效率、好转率及总有效率分别为27.5%、48.0%、75.5%,而对照组分别为14.6%、33.3%、47.9%,2组差别均有统计学意义（P〈0.05,P〈0.01）。结论吡格列酮是治疗2型糖尿病合并脂肪肝较为理想和安全的药物之一。     

Peroxisome proliferator-activated receptor gamma (PPARgamma) activation and its consequences in humans

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the superfamily of nuclear receptors. It binds and is activated by natural polyunsaturated fatty acids, eicosanoids, synthetic thiazolidinediones and related analogues. Biological effects exerted by PPARγ ligands are mostly concerned with differentiation processes, sensitization to insulin and atherogenesis, and are paradigmatically ascribed to PPARγ transactivation of PPARγ-responsive genes. The PPARγ paradigm and its consequences in humans are analyzed here in terms of the tissue specificity of PPARγ, loss and gain of function mutants of PPARγ, PPARγ-responsive genes and clinical effects of PPARγ ligands. Differentiation, as well as some of the atherogenic effects induced by PPARγ ligands, does conform to the PPARγ paradigm. However, sensitization to insulin as well as some of the antiatherogenic effects of PPARγ ligands is not accounted for by PPARγ activation, thus calling for an alternative target for insulin sensitizers.     

Efficacy and safety of glucose-lowering agents in patients with type 2 diabetes: A network meta-analysis of randomized,active comparator-controlled trials

AimAim of the present network meta-analysis (NMA) is the comparison across glucose-lowering drugs (GLA) concerning their effects on glucose control, body weight, hypoglycemia, gastrointestinal adverse events, and quality of life.Data synthesisThis NMA includes randomized clinical trials comparing different head-to-head comparison trials with EMA-approved GLA in type 2 diabetes, with a duration of ≥52 weeks. All drugs have to be administered at the maximal approved dose. Primary endpoints were HbA1c at 12, 52, and 104+ weeks. Secondary endpoints were body weight, quality of life, hypoglycemia, and gastrointestinal disorders. Indirect comparisons of different GLA were performed by NMA choosing metformin as reference. The standardized difference in means (SDM) and Mantel-Haenzel Odds Ratio [MH–OR] (using random-effect models) with 95% Confidence Intervals were calculated for categorical and continuous variables, respectively.We included 68 trials fulfilling all inclusion criteria. At 12 weeks, when considering indirect comparisons, insulin secretagogues (IS) were associated with a significantly greater reduction in comparison with metformin (SDM, ?0.3 [-0.4;-0.2]%); a significantly lower efficacy was observed for pioglitazone. At 52 weeks, IS were no longer associated with a greater reduction of HbA1c; whereas a significant decrease in HbA1c was observed for GLP-1 RA (SDM, ?0.2 [-0.1;-0.3]%). At 104+ weeks, only SGLT-2 inhibitors showed a significantly greater HbA1c reduction (SDM, ?0.2 [-0.1;-0.3]%), whereas sulfonylureas and insulin showed a significantly lower efficacy (SDM, 0.1 [0.0; 0.2]%), and 0.4 [0.3; 0.5]%, respectively).ConclusionsThe results of this meta-analysis should be considered together with evidence on long-term outcomes for selecting the most appropriate drugs for individual patients.     

Energy restriction mimetic agents to target cancer cells: Comparison between 2-deoxyglucose and thiazolidinediones

The use of energy restriction mimetic agents (ERMAs) to selectively target cancer cells addicted to glycolysis could be a promising therapeutic approach. Thiazolidinediones (TZDs) are synthetic agonists of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity but the molecular mechanisms involved in the anticancer action are not yet well understood. Results obtained on ciglitazone derivatives, mainly in prostate cancer cell models, suggest that these compounds could act as ERMAs. In the present paper, we introduce how compounds like 2-deoxyglucose target the Warburg effect and then we discuss the possibility that the PPARγ-independent effects of various TZD could result from their action as ERMAs.