瘦素与胰岛素抵抗

瘦素是由肥胖基因编码的一种多肽激素 ,具有调节能量代谢和抑制食欲的作用。其调节作用由瘦素受体所介导。瘦素受体属于Ⅰ类细胞因子受体家族。Janus酪氨酸蛋白激酶 信号传导与转录激活蛋白 (JAK STAT)途径是瘦素信号转导的主要途径。大多数肥胖患者存在瘦素抵抗 ,瘦素抵抗的发生与多种因素有关。瘦素可抑制胰岛素分泌并拮抗胰岛素的多种生物学作用     

中医药调控JAK/STAT信号通路的研究进展

酪氨酸蛋白激酶/信号转导因子和转录激活因子(JAK/STAT)通路是一条由细胞因子刺激的信号转导通路,参与细胞的增殖、分化、凋亡以及免疫调节等许多重要的生物学过程。细胞因子信号转导抑制因子(SOCS)家族是该通路最重要的抑制信号因子。本文就中医药在调控JAK/STAT、SOCS信号通路的研究做一综述。     

瘦素与胰岛素抵抗

瘦素是由肥胖基因编码的一种多肽激素，具有调节能量代谢和抑制食欲的作用。其调节作用由瘦素受体所介导。瘦素受体属于Ⅰ类细胞因子受体家族。Janus酪氨酸蛋白激酶－信号传导与转录激活蛋白（JAK－STAT）途径是瘦素信号转导的主要途径。大多数肥胖患者存在瘦素抵抗，瘦素抵抗的发生与多种因素有关。瘦素可抑制胰岛素分泌并拮抗胰岛素的多种生物学作用。     

心力衰竭合并恶病质大鼠瘦素及Janus蛋白酪氨酸激酶2/信号传导与转录激活因子3信号转导通路的变化

目的:探讨慢性心力衰竭合并恶病质大鼠血清瘦素水平的变化,并从瘦素受体表达及瘦素信号转导通路探讨其变化的原因,初步阐明心力衰竭恶病质的发生机制,为其治疗寻求新靶点。方法:60只雄性SD大鼠随机挑选15只作为对照组,其余45只大鼠通过注射异丙肾上腺素制作大鼠心力衰竭模型(ISO组,n=36,死亡9只),根据体重变化及超声心动图结果将ISO组分为心力衰竭恶病质亚组(c CHF亚组,n=16)与心力衰竭非恶病质亚组(nc CHF亚组,n=20)。酶联免疫吸附法检测各组大鼠血清瘦素、Janus蛋白酪氨酸激酶2(JAK2)、信号传导与转录激活因子3(STAT3)、细胞因子信号转导抑制因子3(SOCS3)水平;免疫组化法检测大鼠心肌、脂肪组织中瘦素受体的表达情况;逆转录聚合酶链反应(RT-PCR)法检测大鼠脂肪组织中JAK2、STAT3、SOCS3信使核糖核酸(m RNA)表达情况。结果:血清瘦素、JAK2、STAT3水平及脂肪组织JAK2、STAT3表达在nc CHF亚组和c CHF亚组明显高于对照组(P0.05),差异有统计学意义;JAK2、STAT3水平及m RNA表达在c CHF亚组低于nc CHF亚组(P0.05),差异无统计学意义;血清瘦素、SOCS3水平及SOCS3 m RNA表达在c CHF亚组低于nc CHF亚组(P0.05),差异有统计学意义;瘦素受体在大鼠心肌、脂肪组织中的表达,c CHF亚组均高于nc CHF亚组和对照组(P0.05),差异有统计学意义,nc CHF亚组高于对照组(P0.05),差异有统计学意义。结论:高瘦素水平参与心力衰竭的发生,且瘦素水平与受体表达及其JAK2/STAT3信号通路相关蛋白表达的变化相关;瘦素的JAK2/STAT3信号通路可能参与心力衰竭恶病质的发生。     

SOCS-3与胰岛素抵抗

SOCS(suppressor of cytokine signaling)蛋白是通过Janus激酶(JAK)/信号转导与转录激活子(STAT)途径激活的细胞因子信号转导的一个重要的生理抑制剂家族,SOCS-3是该家族成员之一,主要参与负调控生长激素、白细胞介素(IL)-1I、L-2I、L-6、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、催乳素等细胞因子的信号转导。最近研究发现,SOCS-3在胰岛素信号转导中有十分重要的调控功能,本文对其在胰岛素抵抗发生中作用的研究现状作一综述。     

SOCS-3与胰岛素抵抗

SOCS（suppressor of cytokine signaling）蛋白是通过Janus激酶（JAK）/信号转导与转录激活子（STAT）途径激活的细胞因子信号转导的一个重要的生理抑制剂家族,SOCS-3是该家族成员之一,主要参与负调控生长激素、白细胞介素（IL）-1、IL-2、IL-6、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ、催乳素等细胞因子的信号转导.最近研究发现,SOCS-3在胰岛素信号转导中有十分重要的调控功能,本文对其在胰岛素抵抗发生中作用的研究现状作一综述.     

白细胞介素-6和瘦素与脑梗死

IL-6是脑梗死发病过程中起重要作用的炎性细胞因子,主要通过JAK/STAT信号转导途径与瘦素相互作用竞争性抑制瘦素与其受体的结合,导致瘦素抵抗并影响胰岛素的分泌,且可引起血压、血脂和血糖等升高,促进脑梗死发病。     

细胞因子信号转导负调控蛋白

目前已知的SOCS家族共有8个成员,细胞因子信号通路能调节该家族蛋白的表达,而SOCS蛋白通过直接结合活化的JAK激酶或磷酸化的受体抑制JAK/STAT信号转导通路的活性。现利用该家族保守域又得到一系列蛋白,但功能尚不详。     

细胞因子信号转导负调控蛋白——SOCS家族研究进展

目前已知的SOCS家族共有 8个成员 ,细胞因子信号通路能调节该家族蛋白的表达 ,而SOCS蛋白通过直接结合活化的JAK激酶或磷酸化的受体抑制JAK/STAT信号转导通路的活性。现利用该家族保守域又得到一系列蛋白 ,但功能尚不详。     

白细胞介素—6和瘦素与脑梗死

IL-6是脑梗死发病过程中起重要作用的炎性细胞因子，主要通过JAK/STAT信号转导途径与瘦素相互作用竞争性抑制瘦素与其受体的结合，导致瘦素抵抗并影响胰岛素的分泌，且可引起血压、血脂和血糖等升高，促进脑梗死发病。     

Attenuation of leptin and insulin signaling by SOCS proteins.

Leptin and insulin are key hormones involved in the regulation of energy balance and glucose homeostasis. Development of resistance to the action of these hormones, which can occur with age, obesity and inflammation, appears to have a prime role in the pathogenesis of obesity and type 2 diabetes. Specific members of the suppressor of cytokine signaling (SOCS) family of proteins are now thought to have a role in the development of leptin and insulin resistance owing to their ability to inhibit leptin and insulin signaling pathways. In the case of leptin, current evidence suggests that SOCS3 appears to be of particular importance in the development of leptin resistance, whereas the ability to diminish insulin action has been described for several SOCS proteins (SOCS1, SOCS3, SOCS6 and SOCS7).     

Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome.

Insulin resistance, obesity, diabetes, dyslipidemia and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the molecular mechanism of the development of this syndrome is poorly understood. In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1. Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1. The latter leads to dramatic amelioration of hepatic steatosis and hypertriglyceridemia. Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3. This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins. Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins. These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver. Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling.