吸烟与胰岛素抵抗

吸烟可使健康人及糖尿病患者胰岛素敏感性受到急性或慢性损害，导致或加重胰岛素抵制。本文重点介绍目前对吸烟与胰岛素抵抗的研究概况。     

胰岛素抵抗综合征防治进展——胰岛素抵抗与冠心病

流行病学研究证明 ,空腹血浆胰岛素水平升高是冠心病的一个独立预测指标 ,且在非糖尿病个体中尤甚。胰岛素抵抗 (IR)及其代偿性的高胰岛素血症 ,可明显增加个体冠心病的危险性 ,这是因为IR与内皮细胞损伤、平滑肌细胞增殖有密切关系。正常情况下 ,胰岛素作用于血管内皮细胞 ,产生一氧化氮 ,并刺激前列腺素释放 ,抑制内皮素释放 ,使血管扩张。IR时患者内皮细胞功能障碍 ,凝血系统激活 ,纤溶系统受抑制 ,可致脂质沉积、血栓形成和血管平滑肌增殖。巨噬细胞和纤维组织在血管内膜下形成脂肪纹 ,进一步发展为粥样硬化斑块 ,致血管壁增厚 ,管腔…     

瘦素抵抗与胰岛素抵抗

胰岛素抵抗和瘦素抵抗是多种代谢性疾病共同的病理基础, 是引起机体能量代谢紊乱的重要因素. 多项研究发现两者存在交互影响, 但对胰岛素抵抗和瘦素抵抗的探索多是独立进行. 本文拟从两者在多个水平, 多个环节的相互作用作一综述.     

胰岛素抵抗与阿尔茨海默病

胰岛素抵抗(IR)是指各种原因使体内胰岛素水平高于正常而其有效浓度及生物效能减低，导致胰岛素相对不足。IR发生的原因有增龄因素、膳食因素、妊娠、肥胖、运动减少、应激状态、应用某些抗胰岛素作用的药物、种族差异、遗传因素等，其中增龄、膳食、应激状态、肥胖为IR与阿尔茨海默病(AD)的共同病因。IR发生的机制包括胰岛素拮抗剂的作用以及胰岛素与其受体结合到作用于靶分子过程中的任何一环节发生障碍。     

胰岛素抵抗与高血压

已有很多研究显示高胰岛素血症、胰岛素抵抗与血压水平密切相关,但在某些肥胖或非胰岛素依赖型糖尿病(NIDDM)人群却未能发现血浆胰岛素水平与血压的正相关关系,尽管这些人群较非肥胖人群有更为明显的高胰岛素血症。值得注意的是即使在胰岛素与血压不相关的材料中也发现胰岛素抵抗与血压水平正相关。为什么会出现这种现象?有些作者认为是胰岛素抵抗而不是高胰岛素血症原发地与高血压相联系,高胰岛素血症是机体对胰岛素抵抗的代偿,高胰岛素血     

胰岛素抵抗与胰岛素抵抗基因

从胰岛素分泌直到发挥生物学效应的一系列过程中有异常均可能导致胰岛素低抗(IR),包括胰岛素受体及受体前、后的缺陷,葡萄糖体内代谢过程中各个环节的异常等.IR 具有明显的遗传特性,目前对IR相关基因的研究已取得了一定成果,文中简要介绍了目前主要研究的一些IR相关基因.     

胰岛素抵抗综合征防治进展——胰岛素抵抗与脂代谢异常

胰岛素抵抗 (IR)是指整体、器官或组织对胰岛素作用的反应性降低 ,主要表现为胰岛素促进外周组织 (肌肉、脂肪组织 )摄取、利用葡萄糖及抑制肝糖输出的效应减弱 ,需机体分泌更多的胰岛素才能代偿这种缺陷。以IR及其相应高胰岛素血症为基础的代谢综合征是由一组代谢性疾病所组成 ,其中脂代谢异常是代谢综合征的主要组分。1　IR与脂代谢异常的关系IR时 ,脂代谢异常主要表现为游离脂肪酸 (FFA)、甘油三酯 (TG)、极低密度脂蛋白 (VLDL)、小而致密低密度脂蛋白(sLDL)升高 ,高密度脂蛋白 (HDL)降低。从脂肪细胞衍生而来的一系列信号分子…     

miRNA与胰岛素抵抗

IR是T2DM的主要病因之一,但其发病机制至今仍未完全阐明。尽管胰岛素信号传递缺陷被认为在IR发生过程中扮演了重要的角色,但新近研究发现,miRNAs与IR密切相关。因此,对IR相关miRNAs的研究将为进一步阐明IR发病机制提供新的思路,为早期预防和治疗IR提供新的靶点。     

胰岛素抵抗与内皮细胞

过去的观点认为血管内皮是一无活性的内皮细胞层,今天人们已认识到它是一种具有旁分泌和自分泌功能的复杂器官,正常的内皮功能在维持正常的血管功能中起着重要作用,包括维持抗黏附特性,调节动脉血管张力,影响凝血系统。(PanusC.RomJInternMed,2003,41:2733)这些功能是由内皮所产生的血管舒张物质及血管收缩物质介导的,这些物质在生理条件下是保持平衡的。血管舒张物质主要包括一氧化氮(NO)、内皮来源的超极化因子、利钠肽、激肽,血管收缩物质包括血管紧张素Ⅱ(ATⅡ)及内皮素1。NO通过刺激血管平滑肌细胞产生二磷酸环磷鸟苷,发挥舒张血…     

胰岛素受体基因变异与胰岛素抵抗

胰岛素受体基因突变常常引起胰岛素抵抗。它主要通过抑制受体的生物合成，使受体向膜的转运发生障碍，降低受体与胰岛素的亲和力，抑制受体酪氨酸激素酶活性，加速受体的降解，而减少细胞膜表面的胰岛素受体的数目和（或）削弱胰岛素受体的正常功能而最终导致胰岛素抵抗。由于胰岛素受体基因与胰岛素抵抗的密切关系，胰岛素受体基因已成为研究一些与胰岛素抵抗相关疾病的重要的候选基因。有研究推测大约１％￣１０％的非胰岛素依赖型     

Previous hepatitis E virus infection,cirrhosis and insulin resistance in patients with chronic hepatitis C

Background

Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance.

乙型和丙型肝炎病毒感染与肝细胞癌

为探讨乙型和丙型肝炎病毒（ＨＢＶ和ＨＣＶ）感染与肝细胞癌（肝癌）发生的关系，采用ＥＬＩＳＡ和聚合酶链反应（ＰＣＲ）对沈阳地区１１７例肝癌、１０７例肝硬化和４５例血液透析患者血清进行了ＨＢＶ和ＨＣＶ血清标志及ＨＢＶＤＮＡ和ＨＣＶＲＮＡ检测，并采用限制性片段长度多态性对其中７３例ＨＣＶＲＮＡ阳性血清进行了ＨＣＶ基因分型。结果，肝癌组ＨＢＶ感染率（６０７％）显著高于ＨＣＶ感染率（３３３％，Ｐ＜００１），肝硬化组ＨＢＶ感染率（４３９％）明显高于ＨＣＶ感染率（２９０％，Ｐ＜００５）；血液透析组ＨＢＶ和ＨＣＶ重叠感染率（２６７％）明显高于肝硬化组（１０３％，Ｐ＜００５）；各组均以ＨＣＶⅡ型为主（６５２％～８００％），ＨＣＶⅢ型次之（２００％～３１４％）。结果提示：沈阳地区肝癌的诱发因素仍以ＨＢＶ为主，血液透析患者ＨＢＶ和ＨＣＶ重叠感染的机会更大，ＨＣＶⅡ型感染在本地区ＨＣＶ相关性肝癌和肝硬化的发生中可能起主要作用。     

Hepatitis C virus infection in Italian patients with fibromyalgia

We evaluated the prevalence of hepatitis C virus (HCV) infection in Italian patients suffering from fibromyalgia (FM), in comparison with patients affected by non-HCV related rheumatic degenerative disorders. Consecutive patients with FM and a statistically comparable group of patients suffering from peripheral osteoarthritis (OA) or sciatica due to L4-L5 or L5-S1 herniated disc were tested for HCV infection with a third-generation microparticle enzyme immunoassay (MEIA). In the positive cases, a third-generation recombinant immunoblot assay (RIBA) confirmatory test and serum HCV-RNA test were performed. Fisher’s exact test was performed to compare the prevalence of HCV infection (MEIA- and RIBA-positive results) obtained in the two enrolled groups. Enrolled were 152 subjects suffering from FM and 152 patients with peripheral OA or sciatica. Anti-HCV antibodies were found in 7/152 (4.6%) patients suffering from FM and in 5/152 (3.3%) of control subjects. No statistically significant differences in HCV prevalence were detected between cases and controls. Our present report does not confirm previous data indicating an increased prevalence of HCV in FM patients and does not seem to support a significant pathogenetic role of HCV under this condition.     

Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis： Differences and similarities

AIM： To investigate the prevalence of the clinical pa- rameters of insulin resistance and diabetes in patients affected by chronic hepatitis C （CHC） or chronic hepa- titis B （CHB）. METHODS： We retrospectively evaluated 852 consec- utive patients （726 CHC and 126 CriB） who had under- gone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome （MS）, body mass index （BMI）, and apparent disease duration （ADD）. RESULTS： Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biop- sies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis （〉 30%） and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis 〉 30% in CHC, whereas only age and BMI were related to steatosis in CriB. CONCLUSION： These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.     

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.     

Hepatitis B virus and hepatitis C virus infection in healthcare workers

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus(HBV) and 1000000 to hepatitis C virus(HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.     

乙型肝炎病毒rtN238H变异与阿德福韦酯耐药的相关性研究

目的阐明乙型肝炎病毒（HBV）多聚酶/逆转录酶区rtN238H变异对临床产生阿德福韦（ADV）耐药的影响。方法分析了1789例慢性乙型肝炎患者rtN238H变异的发生频率及其与ADV用药的关系;从典型病例患者血清中克隆获得HBV rtN238H变异株并通过回复定点突变获得对应的野生株,分别构建pTriEx-HBV1.1重组表达载体,瞬时转染HepG2细胞。给予转染细胞不同浓度ADV处理,用DNase消化游离DNA后,对上清中成熟病毒颗粒中的HBV DNA进行裂解定量以评价病毒的复制力。结果在1789例乙型肝炎患者中rtN238H变异为181例（10.1%）,其中HBV B基因型感染为151例（83.4%）,C基因型感染为30例（16.6%）;ADV经治和未治患者分别为130例（71.8.%）和51例（28.2%）,其中对ADV治疗产生临床应答（含部分应答）的占82.3%（107/130）,无应答或出现病毒学反跳的占17.7%（23/130）,但与野生株相比,rtN238H变异株对ADV的敏感性和病毒复制力无明显的改变。结论 rtN238H是HBV自然发生的多态性变异,对ADV敏感性和复制力无直接的影响。     

Hepatitis C virus NS5A promotes insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis

AIM: To investigate the mechanisms of insulin resistance in human hepatoma cells expressing hepatitis C virus(HCV) nonstructural protein 5A(NS5A).METHODS: The human hepatoma cell lines,Huh7 and Huh7.5,were infected with HCV or transientlytransfected with a vector expressing HCV NS5 A. The effect of HCV NS5 A on the status of the critical players involved in insulin signaling was analyzed using realtime quantitative polymerase chain reaction and Western blot assays. Data were analyzed using Graph Pad Prism version 5.0.RESULTS: To investigate the effect of insulin treatment on the players involved in insulin signaling pathway,we analyzed the status of insulin receptor substrate-1(IRS-1) phosphorylation in HCV infected cells or Huh7.5 cells transfected with an HCV NS5 A expression vector. Our results indicated that there was an increased phosphorylation of IRS-1(Ser307) in HCV infected or NS5 A transfected Huh7.5 cells compared to their respective controls. Furthermore,an increased phosphorylation of Akt(Ser473) was observed in HCV infected and NS5 A transfected cells compared to their mock infected cells. In contrast,we observed decreased phosphorylation of Akt Thr308 phosphorylation in HCV NS5 A transfected cells. These results suggest that Huh7.5 cells either infected with HCV or ectopically expressing HCV NS5 A alone have the potential to induce insulin resistance by the phosphorylation of IRS-1 at serine residue(Ser307) followed by decreased phosphorylation of Akt Thr308,Fox01 Ser256 and GSK3β Ser9,the downstream players of the insulin signalingpathway. Furthermore,increased expression of PECK and glucose-6-phosphatase,the molecules involved in gluconeogenesis,in HCV NS5 A transfected cells was observed.CONCLUSION: Taken together,our results suggest the role of HCV NS5 A in the induction of insulin resistance by modulating various cellular targets involved in the insulin signaling pathway.     

Hepatitis B virus infection in immigrant populations

Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention.