昼夜节律及骨骼肌节律与肌少症的关系

在生物钟系统中,中枢分子钟基因之间通过相互作用调控外周分子钟基因,进而同步外周器官和组织的昼夜节律.骨骼肌作为人体最大的组织,已被证实除了受中枢时钟的控制,还受到规律运动等其他因素的控制,在骨骼肌的生长发育、力量和功能等方面表现出节律性.研究发现分子钟缺失或缺陷导致的昼夜节律紊乱会损害骨骼肌健康,甚至导致肌少症.此外,...     

微量元素锂与糖代谢的关系

微量元素锂与糖代谢的关系黄列军，周智广，超楚生，胡敏，伍汉文锂是一种具有高度活性的碱性金属元素，分布于机体的体液中，在肝肾中迅速达到稳定平衡，而在肌肉和骨骼中则约需１周才能建立完全平衡。在体内锂不与蛋白结合，亦不进行代谢，９５％以原形从尿中排１９２４...     

糖代谢酶与阿尔茨海默病关系的研究进展

目前为止,阿尔茨海默病(AD)的具体机制仍不十分明确.研究表明,AD患者脑中普遍存在葡萄糖利用降低和代谢异常,并且代谢能力的下降与痴呆程度成正比[1].AD患者在出现认知功能减退以前,大脑皮层的糖代谢就已经出现异常.Wang等[2]也认为糖代谢下降是AD的早期标志,且下降的幅度与痴呆的程度有关.糖代谢障碍与AD关系密切,是导致神经元退变的共同通路,它与AD脑神经元的丢失、老年斑的形成、神经纤维缠结等都有密切的联系.     

Baf60c／Deptor信号通路在肥胖小鼠中连接骨骼肌炎症与糖代谢平衡

2型糖尿病患者骨骼肌胰岛素抵抗与肌纤维代谢由有氧氧化向糖酵解转变相关。然而这种代谢转换开关对于内环境平衡来说是有害还是有益，目前尚未明确。我们最近研究发现，Baf60c／Deptor途径促进肌肉糖酵解代谢，并使小鼠避免了饮食相关的胰岛素抵抗。但在严重胰岛素抵抗状态下，信号的性质对通路的影响以及Baf60c在葡萄糖自稳中的作用仍然未知。     

他汀类药物相关肌病的临床和骨骼肌病理特点

目的 探讨他汀类药物相关肌病(简称他汀肌病)的临床特点及骨骼肌病理改变特点.方法 分析2012年4月至2014年10月就诊于北京大学第一医院并行肌肉活检的9例他汀肌病患者的临床及病理资料.结果 9例患者均口服他汀类药物4d至4年,就诊年龄55 ～74(63 ±6)岁,其中男6例,女3例.3例出现肌痛,6例出现四肢近端为主的肌无力,3例无任何临床症状.所有患者血清肌酸激酶(CK)升高(468 ～8 000 U/L).7例患者行血清肌炎抗体检查,均阴性.6例患者行肌电图检查,2例出现肌源性损害.6例患者行双侧大腿骨骼肌MRI检查,其中2例显示有部分肌群水肿及轻度脂肪化.骨骼肌活检病理主要表现:肌纤维萎缩、坏死、再生、脂肪滴增多,部分患者出现破碎蓝纤维、细胞色素c氧化酶阴性肌纤维及还原型辅酶Ⅰ四氮唑还原酶活性降低,主要组织相容性复合物-Ⅰ在肌纤维膜不同程度表达,补体C5b-9染色显示肌内衣、胞质以及毛细血管少量补体沉积.随访发现,多数(7例)患者停用他汀类药物或换用其他他汀类药物后,症状及CK水平改善,仅2例患者需应用免疫抑制治疗且有效.结论 本组患者中多数(7例)他汀肌病为自限性,停用他汀类药物后可自行好转,个别患者(2例)可出现免疫性坏死性肌肉病,需要应用免疫抑制治疗.     

高尿酸血症与糖代谢异常的关系

生活方式及饮食结构的显著改变,使得高尿酸血症患病率明显增加.尿酸在体内作用相当复杂,目前的临床和基础研究结果提示,高尿酸可通过多种信号通路影响β细胞及其功能、参与胰岛素抵抗的发生,与糖代谢异常密切相关,并可独立预测2型糖尿病的发生.关注二者之间的关系将有益于临床诊治.     

肝硬化 Child-Pugh 分级与糖代谢异常的关系

肝硬化是一种以肝组织弥漫性纤维化、假小叶和再生结节形成为特征的慢性肝病.肝脏功能受损往往影响正常糖代谢,甚至可出现糖耐量减退或糖尿病[1].约60％ ～ 80％肝硬化患者存在高胰岛素血症[2].本文观察肝硬化患者空腹血糖(FPG)、餐后2h血糖(PPG)、血清空腹胰岛素(FINS),胰岛素释放指数(IRI)、胰岛素抵抗指数(IRS)及胰岛素敏感指数(ISI)变化,以明确肝硬化严重程度与糖代谢紊乱之间的关系.     

瘦素与胰岛素抵抗及糖代谢异常的关系

当供给人体的热量多于消耗量而以脂肪形式贮存在体内 ,使人体重量超过标准体重的 2 0 %时称为肥胖。肥胖患者常出现胰岛素抵抗 (ＩＲ) ,血浆胰岛素增高 ,外周组织对胰岛素的敏感性下降。研究表明 ,肥胖是糖代谢异常的重要诱发因素 ,与 2型糖尿病的发生相关。近年来发现 ,肥胖基因的蛋白质产物瘦素 (ｌｅｐｔｉｎ)能调节体重与能量代谢 ,但与ＩＲ及糖代谢异常的关系仍不十分清楚 ,本研究测定 84例受检者血清瘦素含量及其它有关指标 ,探讨瘦素与ＩＲ及糖代谢异常的关系。一、对象和方法1.对象 :84例受检者以往未发现患有糖尿病、甲状腺等内分…     

钙调素与糖代谢

Ca~■-钙调素(CaM)系统是人体细胞内最重要的第二信使系统之一.CaM 与β细胞胰岛素的合成和释放,胰岛素与受体的作用机理均密切相关,并直接参与了对糖代谢一些关键酶活性的调节.CaM 抑制剂——CaM-磷酸二酯酶系统的功能失调在糖尿病发生机理中的作用正引起人们的重视.     

胰岛外的KATP通道与葡萄糖代谢

ATP敏感性钾通道(KATP通道)是将细胞膜电活动与物质代谢联系在一起的重要通道。胰岛α和β细胞膜上的KATP通道通过影响胰升糖素和胰岛素的分泌调节葡萄糖代谢。近年的研究揭示,除胰岛细胞外,下丘脑和骨骼肌细胞膜的KATP通道也与葡萄糖代谢有关。下丘脑KATP通道在中枢对肝脏葡萄糖输出的调节、中枢对低血糖的反应及摄食调节中起一定作用。骨骼肌的KATP通道可影响骨骼肌对葡萄糖的摄取。对胰岛外KATP巯通道的研究,将有助于进一步探讨葡萄糖代谢的调节、糖尿病的发病机制及治疗。     

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

AIMS/HYPOTHESIS: Elevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL/remnants and chylomicrons/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance. METHODS: We studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity, glucose uptake, insulin signalling and intramyocellular lipid (IMCL) content using fully differentiated L6 skeletal muscle cells. RESULTS: Incubation with TGRLs diminished insulin-stimulated glycogen synthesis, glycogen synthase activity, glucose uptake and insulin-stimulated phosphorylation of Akt and glycogen synthase kinase 3. Insulin-stimulated tyrosine phosphorylation of IRS-1, and IRS-1- and IRS-2-associated phosphatidylinositol 3-kinase (PI3K) activity were not impaired by TGRLs, suggesting that these steps were not involved in the lipoprotein-induced effects on glucose metabolism. The overall observed effects were time- and dose-dependent and paralleled IMCL accumulation. NEFA concentration in the incubation media did not increase in the presence of TGRLs indicating that the effects observed were solely due to intact lipoprotein particles. Moreover, co-incubation of TGRLs with orlistat, a potent active-site inhibitor of various lipases, did not alter TGRL-induced effects, whereas co-incubation with receptor-associated protein (RAP), which inhibits interaction of TGRL particles with members of the LDL receptor family, reversed the TGRL-induced effects on glycogen synthesis and insulin signalling. CONCLUSIONS/INTERPRETATION: Our data suggest that the accumulation of TGRLs in the blood stream of insulin-resistant patients may not only be a consequence of insulin resistance but could also be a cause for it.     

p53与物质能量代谢的关系

p53是肿瘤抑制基因,也是参与调节各种反应的转录因子,其表达的蛋白是一种能够激活或者抑制下游基因转录的核蛋白.由于细胞种类、应激状态、所处环境以及细胞内p53表达状态的不同,p53通过多种不同的细胞通路来参与调节糖代谢、脂代谢、能量代谢,甚至与代谢性疾病的发生有一定的关系.     

棕色脂肪组织与糖代谢的关系

研究证实成人体内存在有活性的棕色脂肪组织(BAT).BAT是非颤栗产热和饮食诱导产热的主要器官,其产热作用依赖线粒体内膜的解耦联蛋白1(UCP1).UCP1可使物质氧化与ATP生成解耦联(解耦联呼吸),减少ATP的生成,使能量以热量的形式释放,维持体温与能量的平衡.寒冷暴露、胰岛素、去甲肾上腺素、甲状腺激素等均可诱导UCP1表达使BAT活化,进而促进BAT摄取循环中的葡萄糖,加速循环中葡萄糖的清除.饮食因素以及可诱导BAT活化的因素均可影响BAT对葡萄糖的摄取.     

Skeletal muscle endurance and muscle metabolism in patients with chronic heart failure

BACKGROUND: Alterations in skeletal muscle function are known to contribute to exercise intolerance in patients with chronic heart failure (CHF). OBJECTIVES: To evaluate whether muscle isometric endurance can be objectively measured and whether it is related to skeletal muscle metabolism in CHF. METHODS: Isometric endurance of the vastus lateralis, measured as time to fatigue (T(F)), was evaluated in 25 patients with CHF (55+/-8 years of age [mean +/- SD]) and 18 healthy subjects (HS) (62+/-6 years of age [mean +/- SD]). Median frequency of surface electromyography was obtained from spectral analysis using a fast Fourier transformation. Citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase (HADH), hexokinase (HK) and phosphofructokinase (PFK) activities were determined from the right vastus lateralis muscle. RESULTS: T(F) was lower in CHF patients than in HS (49+/-4 s and 80+/-7 s, respectively; P<0.01). Muscle fatigue was present at the end of the endurance test in both groups (median frequency breakpoint at mid-exercise for both groups [P<0.05]). CS (P<0.01) and HK (P<0.01) activities were lower in CHF patients than in HS, but PFK activity was higher (P<0.05). T(F) correlated significantly with CS (r=0.50), HADH (r=0.42), PFK (r=-0.47) and HK (r=0.41) activities and the PFK/CS ratio (r=-0.39) when both groups were considered, and with HADH (r=0.47) and PFK (r=-0.57) activities for the CHF group alone (all P<0.05). CONCLUSIONS: These results suggest that isometric endurance of the vastus lateralis muscle is reduced in patients with CHF and that it is related to a reduced muscle oxidative capacity.     

Effect of physical training on glucose tolerance and on glucose metabolism of skeletal muscle in anaesthetized normal rats

Summary The effect of physical training on glucose tolerance in vivo and skeletal muscle glucose metabolism in vitro was investigated in normal rats. Treadmill running for 10 days up to 240 min/day led to a decrease of basal and glucose-stimulated plasma insulin levels without major alterations of the IV glucose tolerance (1 g/kg body weight). Swim training of two weeks' duration, i. e. exercise up to 2×75 min/ day, which did not induce significant changes in body composition, skeletal muscle glycogen levels or citrate synthase activity, resulted in a significant improvement of IV glucose tolerance and substantial reductions of basal and glucose-stimulated plasma insulin levels. Associated with this apparent improvement of insulin sensitivity in vivo, significant increases of the insulin-stimulated glucose uptake (+ 55%) and lactate oxidation (+ 78%) in vitro were found on perfusion of the isolated hindquarter of swim-trained animals. It is suggested that mild physical training can improve glucose tolerance and insulin sensitivity in normal rats, at least in part, due to an increase of insulin sensitivity of skeletal muscle glucose metabolism.     

Specificity of insulin signalling in human skeletal muscle as revealed by small interfering RNA

Insulin action on metabolically active tissues is a complex process involving positive and negative feedback regulation to control whole body glucose homeostasis. At the cellular level, glucose and lipid metabolism, as well as protein synthesis, are controlled through canonical insulin signalling cascades. The discovery of small interfering RNA (siRNA) allows for the molecular dissection of critical components of the regulation of metabolic and gene regulatory events in insulin-sensitive tissues. The application of siRNA to tissues of human origin allows for the molecular dissection of the mechanism(s) regulating glucose and lipid metabolism. Penetration of the pathways controlling insulin action in human tissue may aid in discovery efforts to develop diabetes prevention and treatment strategies. This review will focus on the use of siRNA to validate critical regulators controlling insulin action in human skeletal muscle, a key organ important for the control of whole body insulin-mediated glucose uptake and metabolism.     

Imaging of skeletal muscle

Various diagnostic imaging techniques such as sonography, computed tomography, scintigraphy, radiography, and magnetic resonance imaging (MRI) have made possible the noninvasive evaluation of skeletal muscle injury and disease. Although these different modalities have roles to play, MRI is especially sensitive in the diagnosis of muscle disorders and injury and has proved to be useful in determining the extent of disease, in directing interventions, and in monitoring the response to therapies. This article describes how magnetic resonance images are formed and how the signal intensities in T1- and T2-weighted images may be used for diagnosis of the above-mentioned conditions and injuries.