Genetic disruption of protein phosphatase 5 in mice prevents high-fat diet feeding-induced weight gain

The role of serine/threonine protein phosphatase 5 (PP5) in the development of obesity and insulin resistance associated with high-fat diet-feeding (HFD) was examined using PP5-deficient mice (Ppp5c^−/−). Despite similar caloric intake, Ppp5c^−/− mice on HFD gained markedly less weight and did not accumulate visceral fat compared to wild-type littermates (Ppp5c^+/+). On a control diet, Ppp5c^−/− mice had markedly improved glucose control compared to Ppp5c^+/+ mice, an effect diminished by HFD. However, even after 10 weeks of HFD glucose control in Ppp5c^−/− mice was similar to that observed in Ppp5c^+/+ mice on the control diet. Thus, PP5 deficiency confers protection against HFD-induced weight gain in mice.     

Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle

Exercise enhances insulin sensitivity in skeletal muscle, but the underlying mechanism remains obscure. Recent data suggest that alternatively activated M2 macrophages enhance insulin sensitivity in insulin target organs such as adipose tissue and liver. Therefore, the aim of this study was to determine the role of anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2-deoxy glucose uptake was found to be increased in plantaris muscle. This change was associated with increased number of CD163-expressing macrophages (i.e. M2-polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by pretreatment of mice with clodronate-containing liposome abrogated both CD163-positive macrophage accumulation in skeletal muscle as well as the enhancement of insulin sensitivity after exercise, without affecting insulin-induced phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These results suggest that accumulation of M2-polarized macrophages is involved in exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle, independently of the phosphorylation of Akt and AS160 and expression of GLUT4.     

表没食子儿茶素没食子酸酯对高脂饮食大鼠脂肪组织TNF-α表达的影响及意义

目的 探讨表没食子儿茶素没食子酸酯（EGCG）对高脂饮食大鼠脂肪组织中肿瘤坏死因子-α（TNF-α）表达的影响及其与胰岛素敏感性的相关性.方法 将30只SPF级雄性SD大鼠随机分为正常饮食组（ND组,n=10）和高脂饮食组（HFD组,n=20）.喂养16w,当两组大鼠体质量出现显著差异后（P〈0.05）,将HFD组按随机区组原则分为单纯高脂组（HFD组,n=10）和EGCG干预组（HFD＋0.32%EGCG,EGCG组,n=10）.干预16w.留取血清及附睾周脂肪组织.检测每组大鼠空腹血糖（FBG）、胰岛素水平（FINS）及游离脂肪酸（FFAs）,并计算胰岛素抵抗指数（HOMA-IR）;应用Real-time PCR及Western blot方法检测附睾周脂肪组织中TNF-α表达水平.结果 （1）与HFD组相比,EGCG组FINS水平显著下降[分别为（13.83±0.79）mIU/l vs.（31.71±3.61）mIU/l,P〈0.05];HOMA-IR值下降[分别为（3.36±0.31） vs.（7.59±0.99）,P〈0.05];FFAs值亦明显下降[分别为（0.38±0.08）mmol/l vs.（0.81±0.11）mmol/l,P〈0.05];三组大鼠FBG水平无明显统计学差异（P〉0.05）.（2）与ND组相比,HFD组脂肪组织中TNF-αmRNA水平显著升高[分别为（0.0033±0.00070）vs.（0.0010±0.00008）,P〈0.01];而EGCG组较HFD组则明显下降[分别为（0.0018±0.00037）vs.（0.0033±0.00070）,P〈0.05];同时,EGCG组TNF-α蛋白表达量低于HFD组[分别为（0.42±0.09）vs.（0.67±0.09）,P〈0.05];（3）EGCG组与ND组无明显差异（P〉0.05）.结论 EGCG改善高脂饮食大鼠胰岛素敏感性可能与减轻脂肪组织TNF-α介导的炎症状态相关.     

肥胖者脂肪组织中TNF-α表达与脂肪细胞大小的相关性分析

目的探讨肥胖者网膜脂肪和皮下脂肪两处肿瘤坏死因子-α(TNF-α)蛋白的表达与脂肪细胞大小的相关性。方法选取正常体重者16名,中心型肥胖者32名拟行外科手术患者,术中取出网膜脂肪和皮下脂肪标本,测定脂肪细胞大小,采用western blot方法测定TNF-α蛋白表达。结果肥胖者网膜脂肪和皮下脂肪两处TNF-α蛋白的水平均比正常体重对照组表达高(P<0.01),肥胖者网膜脂肪组织TNF-α蛋白表达高于皮下脂肪(P<0.05),同时研究发现肥胖者皮下脂肪细胞和网膜脂肪细胞大小均明显大于正常体重组(P<0.05),且肥胖者网膜脂肪和皮下脂肪两处脂肪组织TNF-α蛋白表达与脂肪细胞大小呈正相关(网膜:r=0.808,P<0.01;皮下:r=0.452,P<0.05)。结论肥胖者网膜脂肪和皮下脂肪细胞增大,在肥胖相关胰岛素抵抗的发生中起到了重要的作用。     

姜黄素对阿尔茨海默病小鼠海马InR和IGF1R表达的影响

目的观察姜黄素对阿尔茨海默病（Alzheimer＇sdisease,AD）模型APP／PS1双转基因小鼠胰岛素受体（insulinreceptor,InR）和胰岛素样生长因子1受体（insulin·likegrowthfactor1receptor,IGF1R）表达的影响。方法将3月龄的APP／PS1双转基因小鼠随机分为模型组、阳性罗格列酮对照组（每日10ms／kg）、姜黄素大（每日400mg／kg）、中（每日200mg／kg）、小剂量组（100mg／kg）,正常组为相同背景非转基因小鼠。灌胃3个月后,应用免疫组织化学和Westernblot方法进行检测。结果InR和IGF1R免疫组化染色,模型组小鼠大脑海马CA1区较正常对照组InR阳性细胞明显增加（P〈0．01）,姜黄素干预组有所恢复;而模型组小鼠大脑海马CA1区较正常对照组IGF1R阳性细胞明显减少（P〈0．01）,姜黄素干预组有所恢复。Western blot检测海马InR和IGF1R的蛋白表达结果与免疫组织化学检测结果一致。结论姜黄素可以使APP／PS1双转基因小鼠海马增加的InR和减少的IGF1R得以恢复,改善APP／PS1双转基因小鼠胰岛素信号转导。     

不同麻醉和术后镇痛方式对中老年胸科手术后胰岛素抵抗的影响

目的：探讨不同麻醉和术后镇痛方式对中老年胸科手术后胰岛素抵抗的影响。方法：中老年胸科手术患者80例随机分为治疗组与对照组各40例,两组都采用开胸手术治疗,于手术结束前30min硬膜外腔给予镇痛,治疗组采用舒芬太尼镇痛,对照组采用地佐辛镇痛。结果：两组镇痛后2h与镇痛后24h的HR和MVP对比差异明显（P〈0．05）,同时对照组不同时间点的组内对比差异明显（P〈0．05）,治疗组组内对比无明显差异。治疗组在镇痛后2h与镇痛后24h的VAS评分都明显少于对照组（P〈0．05）,Ramsay评分治疗组高于对照组（P〈0．05）。治疗组组内不同时间点胰岛素含量和胰岛素敏感性对比无明显差异,而对照组对比差异明显（P〈0．05）,同时镇痛后组间对比也有明显差异（P〈0．05）。结论：相对于地佐辛,舒芬太尼用于中老年胸科手术术后疼痛镇痛效果良好,能有效地抑制胰岛素抵抗与应激反应的发生,有很好的应用效果。     

胰岛素对糖尿病兔牙槽骨缺损修复的影响

目的：探讨胰岛素对糖尿病兔牙槽骨缺损修复治疗的效果,为糖尿病所致的牙周炎提供临床治疗的依据,方法：40只大耳白兔随机分为4组：A组制备健康兔的牙槽骨缺损;B组为胰岛素组,制备健康兔牙槽骨缺损后,用胰岛素治疗;C组为糖尿病组,制备糖尿病兔牙槽骨缺损;D组为糖尿病胰岛素治疗组,制备糖尿病兔牙槽骨缺损后,用胰岛素治疗。每组10只,缺损制备后4、8周各处死5只,对各组成骨情况进行组织学观察及测定。结果：组织学观察A、B、D组修复区可见大量新骨形成,以B组为显著;C组仅见少许成骨,多为纤维组织。新生骨面积比和成骨细胞数在4、8周时均为D组大于c组,B组大于A组,组间差异有统计学意义（P〈0．05）。证明应用胰岛素促进糖尿病兔缺损牙槽骨形成新骨的效果明显。结论：胰岛素能够促进糖尿病兔牙槽骨缺损的戍骨,为,临床上治疗糖尿病并发牙周炎提供一种新的手段。