脂连素球状域与糖尿病及其心血管并发症关系

作为脂连素的活性部位,脂连素球状域能够调节糖脂代谢、改善胰岛素抵抗和保护胰岛β细胞;另外脂连素球状域还具有保护心血管系统和抗炎症的作用。但近年来又有研究认为脂连素球状域具有促炎症的作用,这可能会限制其临床的应用。     

胰岛素抵抗的多囊卵巢综合征患者脂联素检测及其临床意义

<正>多囊卵巢综合征(PCOS)是妇产科常见的内分泌疾病,约30%~70%患者伴有胰岛素抵抗,高胰岛素血症在其发生、发展及转归中具有重要意义[1,2]。脂联素是脂肪细胞分泌的细胞因子,具有抗炎、抗动脉粥样硬化及抗糖尿病的作用,其水平显著降低与胰岛素抵抗存在直接关联[3,4],基于该事实推测脂联素可能在胰岛素抵抗的PCOS患者中具有重要临床价值。本研究检测胰岛素抵抗的PCOS患者血清脂联素水平并研究其临床意     

非诺贝特对高脂饮食诱导胰岛素抵抗大鼠血浆脂联素和内脂素的影响

胰岛素抵抗（insulin resistances，IR）是肥胖和2型糖尿病的重要病理生理特征。非诺贝特是过氧化物酶体增殖物激活受体-α激动剂，具有抗炎、改善胰岛素抵抗和调节脂肪因子分泌的作用”.本研究观察非诺贝特对高脂饮食诱导胰岛素抵抗大鼠的糖代谢、脂联素和内脂素的影响，探讨非诺贝特改善胰岛素抵抗的可能机制。     

代谢综合征患者血清脂联素水平与胰岛素抵抗的相关性研究

目的:探讨代谢综合征患者血清脂联素水平与胰岛素抵抗的关系。方法:选取代谢综合征患者35例,另选健康对照组20例,所有实验对象空腹采血离心取血清测定脂联素、胰岛素、血糖、胰岛素敏感性指数、胰岛素抵抗指数。结果:与对照组相比,代谢综合征组血清脂联素水平、胰岛素敏感性指数显著降低(P<0.01),血清胰岛素、血糖显著升高(P<0.01)。在代谢综合征组中,血清脂联素与胰岛素、血糖、胰岛素抵抗指数呈负相关,与胰岛素敏感性指数呈正相关(P<0.05)。结论:低血清脂联素水平与胰岛素抵抗密切相关。     

中医药治疗2型糖尿病胰岛素抵抗的研究进展

胰岛素抵抗及继发的代谢紊乱是发生2型糖尿病、高脂血症、心血管疾病及代谢综合征的共同发病基础。传统祖国医学中无胰岛素抵抗这一概念,随着对糖尿病及其并发症的研究不断深入,对胰岛素抵抗的发病机制的研究也逐渐加深,越来越多的新型药物对胰岛素抵抗具有改善及调整作用。中医药以其整体观念,通过中药复方进行多途径、多环境、多靶点的作用机制在改善胰岛素抵抗研究方面具有广阔的前景与特殊优势。     

胰腺肾素-血管紧张素系统在胰岛素抵抗和代谢综合征中的作用及机制研究进展

目的：综述胰腺肾素．血管紧张素系统（RAs）在胰岛素抵抗和代谢综合征中的作用及机制。方法：查阅相关文献,总结RAS与胰岛素抵抗和代谢综合征发生的相关因素,如炎症、氧化应激、胰岛B细胞功能、脂联素等之间的关系,以及RAS阻滞引起的这些因素的变化。结果与结论：血管紧张素（Ang）Ⅱ产生可促进炎症发生、降低胰岛血流量、胰岛素分泌,降低脂联素并增加氧化应激,这些可能最终导致胰岛B细胞功能不全和胰岛素抵抗。血管紧张素转换酶抑制剂（ACE）或AngⅡ受体Ⅰ型（ATl．R）阻滞药可减弱AngⅡ对胰岛血流量、胰岛素分泌和氧化应激的影响。胰腺肾素．血管紧张素系统在胰岛素抵抗和代谢综合征中起着重要的作用,RAS阻滞改善葡萄糖稳态的机制可能是增加了胰岛素水平,改善了胰岛素抵抗。     

褪黑素防治2型糖尿病的研究进展

目的：为褪黑素用于2型糖尿病的防治提供参考。方法：查阅2000—2013年国内外相关文献,总结褪黑素对下丘脑-垂体-肾上腺（HPA）轴的调节作用及在改善葡萄糖稳态、胰岛素抵抗中的作用及其机制。结果与结论：褪黑素可以通过不同的作用机制改善2型糖尿病及并发症,具体机制包括：调节下丘脑．垂体．肾上腺轴;调节脂联素、瘦素和游离脂肪酸水平,改善胰岛素信号传导,进而改善胰岛素抵抗;减少胰岛素的过量分泌防止高胰岛素血症的发生;通过其抗氧化能力和抗糖脂毒性保护胰岛B细胞。提示褪黑素具有作为一种改善胰岛素抵抗、治疗2型糖尿病的新型有效药物的潜力。     

米非司酮在胰岛素抵抗形成中对血管内皮功能的影响

目的:观察米非司酮对高脂饮食诱导的胰岛素抵抗大鼠血管内皮功能的影响.方法:用空腹血糖、空腹血胰岛素、胰岛素抵抗指数及胰岛素敏感指数来评价胰岛素抵抗模型是否成功;用血清皮质酮反映胰岛素抵抗形成过程中糖皮质激素的变化;用血清一氧化氮、抗超氧阴离子活力单位、血压、血脂和大鼠离体胸主动脉一氧化氮合酶的变化来反映内皮功能.结果:高脂饮食8周后,模型组大鼠出现胰岛素抵抗并伴随高血糖、高胰岛素血症、血脂异常、血清一氧化氮和抗超氧阴离子活力单位减少、离体胸主动脉一氧化氮合酶活性降低;给予米非司酮后可以明显改善胰岛素抵抗,改善脂代谢紊乱,增加血清一氧化氮(P＜0.01)和抗超氧阴离子活力单位(P＜0.05),增加内皮一氧化氮合酶活性(P＜0.05).结论:SD大鼠高脂饮食8周可以成功复制胰岛素抵抗模型并伴有内皮功能障碍.米非司酮可以明显改善由高脂饮食诱导的胰岛素抵抗和内皮功能紊乱,推测其可能是通过拮抗了糖皮质激素的生物学效应而发挥作用的.     

葛根芩连汤对2型糖尿病大鼠的治疗作用及其机制探讨

为考察葛根芩连汤(GD)抗糖尿病作用及其机制,建立了高脂饲料联合链脲佐菌素(STZ)诱发的大鼠2型糖尿病模型,研究了GD对糖代谢、胰岛素抵抗和氧化应激反应的影响。结果表明,GD可增加模型大鼠肝糖元合成,显著降低空腹血糖和空腹血清胰岛素含量,升高胰岛素敏感指数;增加血清超氧化物歧化酶(SOD)含量,降低丙二醛(MDA)水平;改善胰岛组织和肾组织形态。提示GD可能通过改善糖代谢、改善胰岛素抵抗、提高组织对胰岛素的敏感性和增强机体抗氧化能力,发挥治疗2型糖尿病和保护受损胰岛β细胞的功能。     

脂联素的分子生物学特性及其作用

脂联素（Adiponectin,Adi）为脂肪组织分泌的一种脂肪细胞因子．在动物和人类的实验中证实具有增加脂肪酸氧化、提高葡萄糖摄取量、改善胰岛素抵抗、抗动脉粥样硬化和抗炎的作用。在临床上Adi与肥胖、胰岛素抵抗、Ⅱ型糖尿病及心血管疾病密切相关。     

Adiponectin and its receptors: Partners contributing to the “vicious circle” leading to the metabolic syndrome?

Although already described five years ago, it is only from year 2000, following intensive research in the field of genetics that the adiponectin protein was related with insulin sensitivity, type 2 diabetes and the metabolic syndrome. The story began with a paradox as this protein exclusively secreted by fat tissue was dramatically decreased in patients presenting an excess of fat mass. Later this decrease was reported with insulin resistance and metabolic syndrome associated phenotypes. The search for genetic variants in the adiponectin encoding ACDC gene and epidemio genetic investigations allowed to associate genetic variations of the gene and phenotypic traits of the metabolic syndrome. One of the major points was the correlation of the levels of circulating adiponectin with insulin sensitivity, leading to a better knowledge of the role of adiponectin. Indeed it is now clearly admitted that adiponectin is an insulin sensitizing cytokine. Recently two adiponectin receptors were described and genetic variations in their genes were associated with features of the metabolic syndrome. Interactions of adiponectin with various partners are discussed in view of a better understanding of adiponectin resistance and insulin resistance.     

Vanadium and insulin increase adiponectin production in 3T3-L1 adipocytes.

Both adiponectin, an adipokine secreted by adipocytes, and vanadium compounds, have been extensively shown to enhance insulin sensitivity in vivo and in vitro. In this study we examined whether insulin and vanadyl sulfate (VS) affected adiponectin release and cell content from 3T3-L1 adipocytes, and whether they acted through a similar signaling pathway. Adiponectin cell content, but not release, consistently increased in cells treated with insulin (100 nM) and VS (10 and 50 microM) after 24 h. On the other hand, VS-induced adiponectin release only occurred after 4 days of incubation. The protein kinase B (PKB) inhibitor, NL-71-101, decreased both insulin and VS-induced adiponectin cell content, while neither wortmannin nor LY 294002, inhibitors of phosphatidylinositol 3-kinase (PI3-K), attenuated insulin or VS-induced adiponectin cell content. Furthermore, VS-induced adiponectin accumulation occurred in the presence of AGL2263, an insulin receptor (IR) inhibitor. These studies provide the first evidence that vanadium could exert its insulin sensitizing effects through the stimulation of adiponectin through a PKB-dependent transduction pathway.     

Adiponectin and its receptors: Partners contributing to the “vicious circle” leading to the metabolic syndrome?

Although already described five years ago, it is only from year 2000, following intensive research in the field of genetics that the adiponectin protein was related with insulin sensitivity, type 2 diabetes and the metabolic syndrome. The story began with a paradox as this protein exclusively secreted by fat tissue was dramatically decreased in patients presenting an excess of fat mass. Later this decrease was reported with insulin resistance and metabolic syndrome associated phenotypes. The search for genetic variants in the adiponectin encoding ACDC gene and epidemio genetic investigations allowed to associate genetic variations of the gene and phenotypic traits of the metabolic syndrome. One of the major points was the correlation of the levels of circulating adiponectin with insulin sensitivity, leading to a better knowledge of the role of adiponectin. Indeed it is now clearly admitted that adiponectin is an insulin sensitizing cytokine. Recently two adiponectin receptors were described and genetic variations in their genes were associated with features of the metabolic syndrome. Interactions of adiponectin with various partners are discussed in view of a better understanding of adiponectin resistance and insulin resistance.     

Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine

Genome-wide scanning is a powerful tool to identify susceptible chromosome loci, however, individual chromosomal regions still have many candidate genes. Although cDNA microarray analysis provides valuable information for identifying genes involved in pathogenesis, expression levels of many genes are changed. A novel approach for identification of therapeutic targets is the combination of genome-wide scanning and the use of DNA chips, as shown in Fig. (1). Using DNA chips, we screened for secreted molecules, the expressions of which were changed in adipose tissues from mice rendered insulin resistance. Decreased expression of one of these molecules, adiponectin/Acrp30, correlates strongly with insulin resistance. Interestingly, recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where adiponectin gene is located. Decreasing serum adiponectin levels are associated with increased risk for type 2 diabetes. Interestingly, adiponectin was decreased in insulin resistant rodent models both of obesity and lipoatrophy, and replenishment of adiponectin ameliorated their insulin resistance. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes Adiponectin knockout mice showed insulin resistance and glucose intolerance. In muscle and liver, adiponectin activated AMP kinase and PPARalpha pathways thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated insulin resistance under a high-fat diet. Despite similar plasma glucose and lipid levels on an apoE deficient background, adiponectin transgenic apoE deficient mice showed amelioration of atherosclerosis, which was associated with decreased expressions of class A scavenger receptor and tumor necrosis factor alpha. Finally, cDNA encoding adiponectin receptors (AdipoR1 and R2) have been identified by expression cloning, which facilitates the understanding of molecular mechanisms of adiponectin actions and obesity-linked diseases such as diabetes and atherosclerosis and the designing of novel antidiabetic and anti-atherogenic drugs with AdipoR1 and R2 as molecular targets.     

脂联素与胰岛素抵抗的关系探讨

目的探讨血清脂联素与胰岛素抵抗以及2型糖尿病的关系。方法选择2型糖尿病患者76例,分为非肥胖组34例,肥胖组42例,正常对照组30名,采用酶联免疫分析法检测空腹血糖、胰岛素和脂联素水平。结果正常对照组和糖尿病非肥胖组相比,体重指数(BMI)相同,但稳态模式评估法的胰岛素抵抗指数(HOMA-IR)后者明显大于前者;糖尿病非肥胖组的脂联素水平明显低于正常对照组。糖尿病肥胖组和正常对照组以及糖尿病非肥胖组相比,不论BMI和HOMA-IR,还是脂联素水平差异均有统计学意义。结论2型糖尿病患者血清脂联素水平越降低,胰岛素抵抗越严重;脂联素水平的降低对胰岛素抵抗和糖尿病的发生发展具有促进作用。     

吡格列酮联合胰岛素对2型糖尿病患者脂联素水平的影响

目的观察吡格列酮联合胰岛素治疗2型糖尿病对患者血浆脂联素水平的影响。方法60例2型糖尿病患者随机分为2组,分别给予胰岛素及吡格列酮联合胰岛素治疗,疗程共12周。分别检测和记录2组患者治疗前后空腹血糖(FBG)、糖化血红蛋白(HbA1c)、脂联素以及胰岛素用量,观察吡格列酮对2型糖尿病患者血浆脂联素的影响。结果2组患者治疗后血糖和HbA1c均控制良好,其中观察组胰岛素日需求量明显低于对照组(P<0.05);观察组血浆脂联素水平较对照组明显升高(P<0.05)。结论吡格列酮联合胰岛素治疗2型糖尿病不仅可良好地控制血糖HbA1c,同时增加患者血浆脂联素水平,提高患者对胰岛素的敏感性,减少胰岛素用量。     

The mechanisms by which PPARgamma and adiponectin regulate glucose and lipid metabolism

Obesity, a state of increased adipose tissue mass, is a major cause for type 2 diabetes, hyperlipidemia, and hypertension, resulting in clustering of risk factors for atherosclerosis. Heterozygous PPARgamma knockout mice and KKA(y) mice administered with a PPARgamma antagonist were protected from high-fat diet-induced adipocyte hypertrophy and insulin resistance. Moderate reduction of PPARgamma activity prevented adipocyte hypertrophy, thereby diminution of TNFalpha, resistin, and FFA and upregulation of adiponectin and leptin. These alterations led to reduction of tissue TG content in muscle/liver, thereby ameliorating insulin resistance. Insulin resistance in the lipoatrophic mice and KKA(y) mice were ameliorated by replenishment of adiponectin. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes, but not the obesity of ob/ob mice. Furthermore, targeted disruption of the adiponectin gene caused moderate insulin resistance and glucose intolerance. In muscle, adiponectin activated AMP kinase and PPARgamma pathways, thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated muscle insulin resistance. In the liver, adiponectin also activated AMPK, thereby downregulating PEPCK and G6Pase, leading to decreased glucose output from the liver. In conclusion, PPARgamma plays a central role in the regulation of adipocyte hypertrophy and insulin sensitivity. The upregulation of the adiponectin pathway by PPARgamma may play a role in the increased insulin sensitivity of heterozygous PPARgamma knockout mice, and activation of adiponectin pathway may provide novel therapeutic strategies for obesity-linked disorders such as type 2 diabetes and metabolic syndrome.     

非酒精性脂肪性肝病患者血清脂联素与胰岛素表达水平及其相关性研究

目的 探讨非酒精性脂肪性肝病患者血清脂联素与胰岛素表达水平及其相关性.方法 选择2010年1月至2011年1月自贡市仁济医学中心收治的非酒精性脂肪性肝病患者50例为观察组,同时收集健康志愿者40例为对照组.用酶联免疫吸附测定法检测2组空腹及餐后2h血清脂联素水平,用化学发光法检测空腹及餐后2h胰岛素表达水平,并进行相关性分析.结果 观察组和正常对照组空腹脂联素水平分别为（912 ±29）、（1 033±53）μg/L,组间差异有统计学意义（P＜0.05）;空腹胰岛素水平分别为（13.8±1.0）、（7.3±1.0）mU/L,组间差异有统计学意义（P＜0.01）.观察组和正常对照组餐后2h脂联素水平分别为（854 ±38）、（1 010±48）μg/L,组间差异有统计学意义（P＜0.05）;餐后2h胰岛素水平分别为（112 ±23）、（28 ±3） μg/L,组间差异有统计学意义（P＜0.01）.相关性分析显示,非酒精性脂肪性肝病患者空腹及餐后2h脂联素与胰岛素水平均呈负相关（空腹：r=-0.328,P=0.020;餐后2 h：r=-0.391,P =0.005）.结论 非酒精性脂肪性肝病进展的同时伴随着胰岛素及脂联素水平的变化,二者呈负相关,这种负相关可能以餐后2h更明显.