抵抗素——联系2型糖尿病与肥胖的新激素

大多数2型糖尿病以胰岛素抵抗为主，同肥胖高度相关。最近的研究显示，脂肪细胞分泌的一种信号分子－－抵抗素（Resistin)参与了饮食诱导或遗传性肥胖小鼠胰岛素抵抗的发生。抵抗素mRNA的表达可被噻唑烷二酮类药物抑制，成为联系肥胖与胰岛素抵抗的中介环节之一。它的发现可能为2型糖尿病的治疗提供一个新的靶点。     

抵抗素——联系2型糖尿病与肥胖的新激素

大多数 2型糖尿病以胰岛素抵抗为主 ,同肥胖高度相关。最近的研究显示 ,脂肪细胞分泌的一种信号分子———抵抗素 (Resistin)参与了饮食诱导或遗传性肥胖小鼠胰岛素抵抗的发生。抵抗素mRNA的表达可被噻唑烷二酮类药物抑制 ,成为联系肥胖与胰岛素抵抗的中介环节之一。它的发现可能为 2型糖尿病的治疗提供一个新的靶点。     

Resistin在脂肪与胰岛素抵抗之间的作用

以胰岛素抵抗为特征的 2型糖尿病正成为全球关注的健康问题 ,而疾病流行调查表明 ,2型糖尿病肥胖患者的比例超过80 % ,这说明胰岛素抵抗与肥胖即脂肪细胞之间具有密切的关系。与肥胖相关的胰岛素抵抗不仅表现为 2型糖尿病 ,还有脂质代谢紊乱、异常高血凝状态及心血管疾病等[1 ] 。在探讨肥胖与胰岛素抵抗之间关系的研究中 ,Steppan等[1 ] 发现一种新的由脂肪细胞分泌的蛋白 ,他们称之为 Resistin(抗素 ) ,意为引起胰岛素抵抗的物质 (也有称之为 Fizz3)。随后围绕 Resistin进行了一系列研究 ,本文将研究的结果综述如下。一、Resistin的发现…     

2型糖尿病患者血浆抵抗与胰岛素抵抗胰岛B细胞功能的研究

目的了解2型糖尿病(T2DM)患者血浆抵抗素(Resistin)质量浓度的改变,并探讨与胰岛素抵抗、胰岛B细胞功能的关系。方法2004-01~2004-10选取苏北医院测定了64例2型糖尿病和30名正常对照组的血浆Resistin、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、空腹血浆胰岛素(FINS)、血脂、体重指数(BMI),计算胰岛素抵抗指数(HOMA-IR)及B细胞功能指数(HOMA-B)。比较Resistin质量浓度的改变及与其它因素的相关性。结果肥胖的糖尿病组与正常对照组比较Resistin明显升高,差异有统计学意义。而在肥胖的糖尿病组对非肥胖糖尿病组,以及非肥胖的糖尿病组对正常对照组的比较中,Resistin数值差异无统计学意义。在糖尿病患者中,血浆Resistin与BMI、HOMA-IR呈正相关,与FBG、FINS、HbA1c、HDL-c、LDL-c、TG、TC及HOMA-B相关性不明显。结论糖尿病患者血浆Resistin质量浓度与体内脂肪容积、胰岛素抵抗有一定的关系,在胰岛素抵抗和2型糖尿病的产生中可能起一定的作用。     

抵抗素--一种与肥胖及糖尿病有关的重要激素

抵抗素（resistin)是脂肪细胞分泌的一种多肽类激素，其基因特异表达于白色脂肪组织。Resistin可能是联系肥胖与胰岛素抵抗及糖尿病的重要信号，多种因素影响resistin的基因表达。目前对resistin的作用仍存在争议，尚待进一步研究。     

032 抵抗素为人类致动脉粥样硬化相关炎症标记物之一

抵抗素（Resistin）属一种血浆蛋白质，并能诱发啮齿类动物体内产生胰岛素抵抗。晚近报道发现，在人类和啮齿类动物伴肥胖和胰岛素抵抗者中循环内抵抗素水平明显升高。在啮齿类动物中，抵抗素主要由脂肪细胞和巨噬细胞产生，推测在人类亦然。综合脂肪细胞和巨噬细胞功能提示，抵抗素可提供与人类肥胖、炎症和致动脉粥样硬化三者间相关联的独特的内在联系。本文拟就抵抗素与人类致动脉粥样硬化相关炎症间关系进行了分析。     

本刊2006年第1期部分文题介绍

1．药物相关性肥胖的研究进展2．内源性大麻素系统与肥胖3．增食欲素与能量平衡4．促酰基化蛋白与能量代谢的研究进展5．Resistin最新研究进展6．对抵抗素作用及作用机制的争议7．血管生成素样蛋白3对脂质代谢及胰岛素抵抗的影响8．代谢综合征的诊断问题9．AMPK与胰岛β细胞功能10．     

抵抗素为人类致动脉粥样硬化相关炎症标记物之一

抵抗素(Resistin)属一种血浆蛋白质,并能诱发啮齿类动物体内产生胰岛素抵抗。晚近报道发现,在人类和啮齿类动物伴肥胖和胰岛素抵抗者中循环内抵抗素水平明显升高。在啮齿类动物中,抵抗素主要由脂肪细胞和巨噬细胞产生,推测在人类亦然。综合脂肪细胞和巨噬细胞功能提示,抵抗素可提供与人类肥胖、炎症和致动脉粥样硬化三者间相关联的独特的内在联系。本文拟就抵抗素与人类致动脉粥样硬化相关炎症间关系进行了分析。     

Adiponectin--一种新的脂肪细胞因子

脂肪组织能分泌一系列脂肪细胞因子(adipocytokines)参与机体的能量代谢，并与肥胖、胰岛素抵抗及其并发症密切相关。新近又发现一种脂肪细胞因子，即脂联素(adi—ponectin)，它是脂肪组织特异性分泌的具有类似胶原结构的蛋白，在肥胖、胰岛素抵抗、2型糖尿病及动脉粥样硬化的患者其浓度明显低于正常人，被认为是胰岛素抵抗和糖尿病大血管病变的保护因子。     

肥胖状态下单核细胞趋化因子-1表达与胰岛素抵抗

近年来炎症学说在与肥胖相关的胰岛素抵抗发病机制中的作用备受关注。研究发现,单核细胞趋化因子-1作为巨噬细胞的特异性趋化因子,它在胰岛素抵抗个体的脂肪、骨骼肌和肾脏等靶组织中高表达。单核细胞趋化因子-1除了可以刺激机体发生适当的免疫反应,还介导与肥胖相关的慢性炎症反应。因此它在肥胖及胰岛素抵抗的发生和发展中起重要作用。     

Resistin - a mediator of obesity-associated insulin resistance or an innocent bystander?

The objective of this review is to summarize the current evidence of a novel adipocytokine, resistin. Resistin is a novel peptide hormone that belongs to a family of tIssue-specific resistin-like molecules originally named for its resistance to insulin. Although a seminal proposal by Steppan et al. suggested resistin to be a hormone that links obesity to diabetes, several studies have subsequently been published supporting the concept that insulin resistance and obesity are actually associated with a decreased resistin expression. Resistin expression is regulated by a variety of agents and hormones, including thiazolidinediones, insulin, tumor necrosis factor alpha and growth hormone. Studies about their role in the regulation of resistin expression are, however, inconsistent in many cases. Experiments in humans have shown no differences in resistin expression between normal, insulin-resistant or type 2 diabetic samples. However, some recent genetic studies have demonstrated an association between resistin and insulin resistance and obesity. In addition, regional variation in the expression of resistin mRNA and protein levels in humans is an interesting finding with the highest levels found in the abdominal depot. In conclusion, resistin is a fascinating new hormone for which a definite role in metabolism will be revealed in the near future.     

对抵抗素在肥胖性胰岛素抵抗中作用及作用机制的争议

抵抗素是近年来发现的一种脂肪细胞分泌的多肽类信号分子,最初发现在肥胖小鼠中血清抵抗素水平上升,免疫中和血清抵抗素能改善胰岛素的敏感性,因此认为它可能是联系肥胖和胰岛素抵抗的关键因子。但是,后来有学者发现肥胖鼠白色脂肪组织中抵抗素mRNA水平下降,这与抵抗素主要来源于脂肪细胞相矛盾,而且大多数的人类实验都发现血清抵抗素水平上升与胰岛素抵抗并不相关。因此,目前对于抵抗素和胰岛素抵抗之间的关系尚存在很大争议。     

抵抗素与胰岛素抵抗

抵抗素是一种多肽激素 ,可能是联系肥胖与胰岛素的重要信号分子 ,与胰岛素抵抗的发生有关 ,从而可能与血管性疾病的发生发展有关。多种因素可影响抵抗素的表达水平。     

抵抗素与炎症、动脉粥样硬化研究进展

抵抗素最初被认为是联系肥胖与胰岛素抵抗、2型糖尿病的脂肪细胞因子。然而近年来研究发现其在人体主要与炎症有关,抵抗素不仅促进炎症的发生,而且炎症因子也可影响抵抗素的表达。动脉粥样硬化是一种慢性亚临床性炎症,大量的研究表明抵抗素与动脉粥样硬化相关。抵抗素通过局部和全身炎症作用诱导内皮功能失调、巨噬细胞的脂质沉积以及平滑肌增殖迁移,从而促进动脉粥样硬化的发生发展。     

抵抗素与肥胖及2型糖尿病的关系

目的探讨抵抗素与肥胖及2型糖尿病(T2DM)的相关性。方法正常人(NC)80例、单纯肥胖(Ob)67例、T2DM77例、伴肥胖的T2DM(Ob DM)102例,测定其血清抵抗素、真胰岛素、胰岛素原、胰升糖素、空腹血糖、血脂及血压等水平,记录身高、体重等。结果四组抵抗素水平差异无统计学意义(P>0.05);抵抗素与胰岛β细胞功能、胰岛素敏感性也无相关性(P>0.05);在Ob、DM及Ob DM组抵抗素与TC呈正相关(r=0.35,0.33,0.38,P<0.05);在Ob及Ob DM组抵抗素与腰臀比呈正相关(r=0.36,0.27,P<0.05);在Ob组抵抗素与PI呈正相关(r=0.37,P<0.05)。结论抵抗素与T2DM无相关性,但可能影响肥胖及糖尿病患者的脂质代谢及胰岛素抵抗的形成。     

Changes in glycemia by leptin administration or high- fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis

Resistin is an adipose-derived hormone that has been proposed as a link among obesity, insulin resistance, and diabetes. In agreement with a role of resistin in insulin resistance, the administration of recombinant resistin led to glucose intolerance in mice and impaired insulin action in rat liver. However, the regulation of resistin expression by physiological conditions, hormones, or agents known to modulate insulin sensitivity does not always support the association between resistin and obesity-induced insulin resistance. In the present study we investigated the effects of leptin administration on adipose resistin expression in insulin-resistant and obese ob/ob mice. We show that the expression of resistin mRNA and protein in adipose tissue is lower in ob/ob than in wild-type control mice, in agreement with the reduced adipocyte resistin mRNA level reported in several models of obesity. Leptin administration in ob/ob mice resulted in improvement of insulin sensitivity concomitant with a decrease in resistin gene expression. The lack of effect of leptin on resistin in db/db mice indicated that the leptin inhibitory action on resistin expression requires the long leptin receptor isoform. In addition, we demonstrated that the effect of leptin on resistin expression was centrally mediated. High-fat feeding in C57BL/6J wild-type mice, which is known to induce the development of obesity and insulin resistance, produced an increase in resistin expression. Interestingly, in both ob/ob and high fat-fed mice we obtained a striking positive correlation between glycemia and resistin gene expression. In conclusion, our results demonstrate that leptin decreases resistin expression and suggest that resistin may influence glucose homeostasis.     

老年糖尿病患者血浆抵抗素与胰岛素抵抗关系的研究

目的　了解老年糖尿病患者血浆抵抗素的浓度及其与肥胖、胰岛素敏感性、血糖、血脂的关系。　方法　选择 5 1例老年 2型糖尿病患者和 4 2例健康老年人 ,分别分为肥胖组和非肥胖组 ,用竞争性酶联免疫吸附法测定各组空腹血浆抵抗素水平 ,同时检测空腹血糖、空腹胰岛素、血脂、胰岛素敏感指数 ,测量受试对象腰围、臀围、腰臀比。　结果　在对照组和糖尿病组中 ,肥胖组空腹血浆抵抗素水平显著高于非肥胖组 (P <0 0 5 ) ;糖尿病非肥胖组空腹血浆抵抗素水平显著高于对照非肥胖组 (P <0 0 1) ,但与对照肥胖组比较 ,差异无显著性 ;糖尿病肥胖组空腹血浆抵抗素水平显著高于对照肥胖组 (P <0 0 5 )。抵抗素与体质指数呈正相关关系 (r =0 2 5 ,P <0 0 5 ) ,与胰岛素敏感指数及空腹胰岛素呈负相关关系 (r=- 0 32、- 0 35 ,P <0 0 5 )。而抵抗素与空腹血糖、各项血脂指标、年龄、性别及腰臀比之间无明显相关性。　结论　在肥胖发展为糖尿病的过程中 ,抵抗素可能参与了胰岛素抵抗 ,并有可能成为诊断胰岛素抵抗的指标之一。     

A paradox： Insulin inhibits expression and secretion of resistin which induces insulin resistance

AIM： To confirm whether insulin regulates resistin expression and secretion during differentiation of 3T3-L1 preadipocytes and the relationship of resistin with insulin resistance both in vivo and in vitro. METHODS： Supernatant resistin was measured during differentiation of 3T3-L1 preadipocytes. L6 rat myoblasts and hepatoma cell line H4IIE were used to confirm the cellular function of resistin. Diet-induced obese rats were used as an insulin resistance model to study the relationship of resistin with insulin resistance. RESULTS： Resistin expression and secretion were enhanced during differentiation 3T3-L1 preadipocytes. This cellular differentiation stimulated resistin expression and secretion, but was suppressed by insulin. Resistin also induced insulin resistance in H4IIE hepatocytes and L6 myoblasts. In diet-induced obese rats, serum resistin levels were negatively correlated with insulin sensitivity, but not with serum insulin. CONCLUSION： Insulin can inhibit resistin expression and secretion in vitro, but insulin is not a major regulator of resistin in vivo. Fat tissue mass affects insulin sensitivity by altering the expression and secretion of resistin.     

Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans

Aims/hypothesis Resistin is thought to be an important link between obesity and insulin resistance. It has been suggested that genetic polymorphism in the promoter of resistin gene is a determinant of resistin mRNA expression and possibly associated with obesity and insulin resistance. In this study, we investigated the association between the genotype of resistin promoter and its plasma concentrations.Methods We examined g.-537A>C and g.-420C>G polymorphisms in the resistin promoter and measured plasma resistin concentrations in Korean subjects with or without Type 2 diabetes. We also did haplotype-based promoter activity assays and the gel electrophoretic mobility shift assay.Results The –420G and the –537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with haplotype A-G (–537A and –420G) had significantly higher plasma resistin concentrations than the others. Haplotype A-G had modestly increased promoter activity compared to the other haplotypes. Electrophoretic mobility shift assay showed that the –420G allele is specific for binding of nuclear proteins from adipocytes and monocytes. However, none of the two polymorphisms were associated with Type 2 diabetes or obesity in our study subjects.Conclusions/interpretation Polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.Abbreviations HOMA-IR homeostasis model assessment of insulin resistance - EMSA electrophoretic mobility shift assay - OR odds ratio An erratum to this article can be found at Y.M. Cho and B.-S. Youn contributed equally to this work