部分炎症因子与胰岛素抵抗

近年来许多研究发现,胰岛素抵抗人群中某些炎症标志物如白介素(IL)-6、肿瘤坏死因子(TNF)-α、C反应蛋白(CRP)等血浆浓度明显升高,它们可通过影响胰岛素受体酪氨酸磷酸化、抑制胰岛素受体信号转导、降低葡萄糖转运体(GLUT)4 mRNA的表达水平、影响血脂代谢、升高游离脂肪酸水平而影响胰岛素的作用及葡萄糖代谢,与胰岛素抵抗密切相关。它们尚可通过与瘦素、脂联素等细胞因子的相互作用参与胰岛素抵抗的发生。     

阿托伐他汀对老年早期糖尿病肾病患者外周血NF-κB和胰岛素抵抗的影响

目的观察阿托伐他汀对老年早期糖尿病肾病患者外周血单个核细胞中核因子-κB(NF-κB)P65的磷酸化水平和血清hs-CRP、TNF-α、IL-6、IL-1β炎症因子以及胰岛素抵抗的影响.方法选择66例老年早期2型糖尿病患者随机分为糖尿病常规治疗组(对照组,n=31)及糖尿病常规治疗联合阿托伐他汀干预组(治疗组,n=35),比较两组治疗前后NF-κB、血清hs-CRP、TNF-α、IL-6、IL-1β及胰岛素抵抗指数(HOMA-IR)的变化.结果治疗12周后,治疗组外周血NF-κB水平、血清炎症因子、HOMA-IR显著下降(P<0.05),对照组无明显变化(P>0.05).结论阿托伐他汀可降低糖尿病肾病患者炎症水平,改善胰岛素抵抗.     

部分炎症因子与胰岛素抵抗

近年来许多研究发现，胰岛素抵抗人群中某些炎症标志物如白介素(IL)-6、肿瘤坏死因子(TNF)-α、C反应蛋白(CRP)等血浆浓度明显升高，它们可通过影响胰岛素受体酪氨酸磷酸化、抑制胰岛素受体信号转导、降低葡萄糖转运体(GLUT)4 mRNA的表达水平、影响血脂代谢、升高游离脂肪酸水平而影响胰岛素的作用及葡萄糖代谢，与胰岛素抵抗密切相关。它们尚可通过与瘦素、脂联素等细胞因子的相互作用参与胰岛素抵抗的发生。     

细胞因子信号转导抑制因子3与白细胞介素6、胰岛素抵抗的关系

细胞因子信号转导抑制因子3（SOCS-3）是白细胞介素6（IL-6）信号转导的负调节因子。研究发现血清IL-6水平与胰岛素抵抗相关，而且可以诱导SOCS03的基因转录。因此，SOCS03mRNA的高表达可能是IL-6介导胰岛素抵抗发生的机制之一。     

结直肠腺瘤性息肉患者血尿酸、炎症因子与胰岛素抵抗的相关性研究

[目的]探讨结直肠腺瘤性息肉患者血尿酸、炎症因子水平与胰岛素抵抗之间的相关性。[方法]选取175例结直肠腺瘤性息肉患者(腺瘤组)及100例健康者(对照组),收集一般临床资料,检测2组患者血尿酸、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及胰岛素抵抗指数(HOMA-IR)水平。[结果]腺瘤组血尿酸、TNF-α、IL-6及HOMA-IR水平高于对照组(P<0.05);根据腺瘤病理性质将腺瘤组进一步分为管状腺瘤、绒毛状腺瘤及管状绒毛状腺瘤3个亚组进行比较,各亚组血尿酸、hs-CRP、TNF-α、IL-6及HOMA-IR水平比较差异无统计学意义(P>0.05)。相关分析显示HOMA-IR与血尿酸、TNF-α、IL-6呈正相关(P<0.05)。[结论]结直肠腺瘤性息肉患者胰岛素抵抗与血尿酸及炎症因子升高相关。     

心脑舒通胶囊对冠心病患者胰岛素抵抗及炎症因子的干预作用

目的探讨心脑舒通胶囊对冠心病患者胰岛素抵抗及炎症因子的干预作用。方法共观察冠心病患者86例,随机分为治疗组(43例)和对照组(43例)。同时选取健康体检者30名作为正常组。治疗组和对照组均予西药常规基础治疗,治疗组再给予心脑舒通胶囊口服,疗程共8周。检测干预前治疗组、对照组、正常组及干预后治疗组、对照组空腹血糖(FBG)、空腹胰岛素(FINS)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、高敏C反应蛋白(hs-CRP)等指标,计算胰岛素抵抗指数(HOMA-IR)。结果治疗前两组冠心病患者FINS、HOMA-IR及TNF-α、IL-6、hs-CRP较正常组显著增加(P0.05),治疗后治疗组FINS、HOMA-IR及TNF-α、IL-6、hs-CRP较治疗前均有显著降低(P0.05或P0.01);对照组TNF-α较治疗前有所下降(P0.05),FBG、FINS、HOMA-IR及IL-6、hs-CRP较治疗前均无统计学意义。结论冠心病患者存在明显的胰岛素抵抗及亚临床炎症,心脑舒通胶囊可以改善冠心病患者的胰岛素抵抗,抑制炎症反应,这可能是其治疗冠心病的机制之一。     

炎症因子在正常个体向2型糖尿病转化中的作用

炎症因子对正常个体向2型糖尿病（T2DM）的转化中可能起重要作用，是T2DM发生的重要预测因子。炎症因子可能通过干扰胰岛素信号转导，引起胰岛素抵抗（IR）和β细胞的功能缺陷，导致T2DM发生。炎症因子与T2DM关联的证据来自大量临床流行病学的研究。主要涉及到的炎症因子有TNF-α、IL-6、CRP、PAI-1等。     

替米沙坦对胰岛素抵抗大鼠早期炎症因子IL-6及血脂的影响研究

目的采用替米沙坦对胰岛素抵抗大鼠进行干预,观察其对胰岛素抵抗大鼠心肌早期炎症因子IL-6及血脂的影响。方法建立大鼠胰岛素抵抗模型,应用替米沙坦进行干预。生化检测血清胰岛素及血脂水平,免疫组化法检测心肌IL-6水平,所有资料以SPSS13.0统计软件进行分析,连续性计量资料,数据以士s表示,两组间的比较采用t检验。结果葡萄糖输注率:干预组明显高于非干预组而仍明显低于对照组(P<0.05);血脂:非干预组TC、TG、LDL-C更加明显高于对照组,高于干预组,HDL-C则相反(P=0.00 0.05);炎症因子IL-6的表达:试验中在空白对照组心肌中未见表达,干预组与未干预组间相比有显著性差异(P<0.05)而与空白对照组间无统计学差异。结论胰岛素抵抗状态下大鼠心肌IL-6表达增强;ARB除了具有控制血糖及降低血脂的作用,同时能改善胰岛素抵抗状态;ARB可以改善胰岛素抵抗状态的慢性炎症反应。     

肿瘤坏死因子α和白细胞介素6致脂肪细胞胰岛素抵抗的不同机制

细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)分别作用于3T3-L1细胞6h和72h,观察对葡萄糖摄取和胰岛素信号转导的影响。两者作用72h抑制胰岛素刺激的葡萄糖摄取、胰岛素受体底物1 (IRS-1)酪氨酸及蛋白激酶B(PKB)磷酸化,并使IRS-1表达下降。TNF-α作用6h增加IRS-1丝氨酸307磷酸化。提示IL-6和TNF-α致胰岛素抵抗的作用机制不尽相同。     

吡格列酮治疗对2型糖尿病合并代谢综合征患者胰岛素抵抗和炎性因子的影响

目的观察吡格列酮治疗对2型糖尿病合并代谢综合征患者胰岛素抵抗、炎症因子和血糖的影响,初步探讨胰岛素抵抗的可能发生机制,及其与炎性因子白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)的关系。方法选取我院收治的2型糖尿病合并代谢综合征患者110例为观察对象,随机为观察组(60例)和对照组(50例)。在常规治疗基础上,观察组口服吡格列酮治疗,对照组患者口服二甲双胍治疗。检测比较两组患者治疗前和治疗3个月后血清IL-6、TNF-α、空腹血糖、餐后2小时血糖、空腹胰岛素水平以及胰岛素敏感指数和胰岛素抵抗指数。结果治疗前,两组患者血清IL-6、TNF-α水平、空腹血糖、餐后2h血糖、空腹胰岛素、胰岛素敏感指数以及胰岛素抵抗指数比较,差异均无统计学意义(P0.05)。治疗3个月后,观察组患者血清IL-6、TNF-α水平、空腹血糖、餐后2h血糖、胰岛素敏感指数以及胰岛素抵抗指数均显著低于对照组,空腹胰岛素水平高于对照组,差异均具有统计学意义(P0.05)。结论吡格列酮可能会通过调节糖尿病患者体内炎性因子的水平,稳定内皮细胞功能,从而改善胰岛素抵抗,降低患者血糖水平。     

Roles of interleukin 17 in angiotensin II type 1 receptor-mediated insulin resistance

Interleukin 17 (IL-17) is known to contribute to the pathogenesis of hypertension, atherosclerosis, and adipocyte differentiation; however, the roles of IL-17 in glucose metabolism remain to be elucidated. Angiotensin II type 1 receptor blockers improve insulin resistance at least in part because of the amelioration of inflammation. Therefore, we examined the possible roles of IL-17 in the pathogenesis of insulin resistance in type 2 diabetes mellitus using a mouse model, KK-Ay, and angiotensin II type 1 receptor-mediated insulin resistance. KK-Ay mice were administered control-IgG(2A) or anti-IL-17 antibody 5 times at a dose of 100 μg every second day by IP injection. KK-Ay mice were administered telmisartan for 2 weeks. C57BL/6J mice treated with angiotensin II infusion for 2 weeks were administered telmisartan or hydralazine. Insulin resistance was evaluated by oral glucose tolerance test, insulin tolerance test, and uptake of 2-[(3)H]deoxy-d-glucose in peripheral tissues. Serum IL-17 concentration in KK-Ay mice was significantly higher than that in C57BL/6J mice. Treatment of KK-Ay mice with anti-IL-17 antibody significantly increased 2-[(3)H]deoxy-d-glucose uptake in skeletal muscle but not in white adipose tissue and attenuated the increase in blood glucose level after a glucose load. Blockade of IL-17 enhanced the expression of adipocyte differentiation markers and adiponectin. Treatment with telmisartan decreased serum IL-17 concentration in KK-Ay and ameliorated angiotensin II-induced insulin resistance with a decrease in serum IL-17 level in C57BL/6J. In conclusion, IL-17 could play an important role in the pathogenesis of angiotensin II type 1 receptor-induced insulin resistance.     

Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients

Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position -174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6-174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 -174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C- (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C- carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6-174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance "IL-6-sensitive", while C- carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.     

Muscle-derived IL-6 improved insulin resistance of C2C12 cells through activating AMPK and inhibiting p38MAPK signal pathway in vitro

International Journal of Diabetes in Developing Countries - This paper was to probe into whether IL-6 improved insulin resistance by AMPK and p38MAPK signal pathway. The C2C12 cell lines were...     

Prolonged interleukin-6 administration enhances glucose tolerance and increases skeletal muscle PPARalpha and UCP2 expression in rats

Chronic elevations in interleukin (IL)-6 have been associated with insulin resistance, but acute IL-6 administration can enhance insulin sensitivity. Our aim was to exogenously administer IL-6 to rats to elicit either chronic or repeated acute elevations in systemic IL-6. We hypothesized that a continuous elevation of IL-6 would inhibit glucose tolerance and insulin sensitivity while acute intermittent elevations would improve it. Male Wistar rats were treated for 14d with recombinant human IL-6 (2.4 microy) or saline administered either by miniosmotic pump (continuous IL-6) or via twice-daily injection (intermittent IL-6). Glucose and insulin tolerance tests were performed following 14-d treatment and 24 h later rats were administered a bolus of insulin (150 mU/g) or saline intraperitoneally. Approximately, 10 min after insulin injection soleus, gastrocnemius and liver were excised and rapidly frozen in liquid nitrogen for subsequent metabolic measures. Irrespective of the mode of delivery, IL-6 treatment increased basal insulin sensitivity, as measured by the homeostatic model assessment of insulin resistance, and enhanced glucose clearance during an i.p. glucose tolerance test. IL-6 increased circulating fatty acids, but did not increase triglyceride accumulation in either skeletal muscle or liver, while it increased the protein expression of both PPARalpha and UCP2 in skeletal muscle, suggesting that IL-6 can enhance fat oxidation via mitochondrial uncoupling. These data demonstrate that, irrespective of the mode of delivery, IL-6 administration over 2 weeks enhances glucose tolerance. Our results do not support the notion that prolonged chronically elevated IL-6 impairs insulin action in vivo.     

电针对胰岛素抵抗模型大鼠血管内皮NF-κB通路的影响

目的观察电针对高脂诱导的胰岛素抵抗(IR)模型大鼠血管内皮炎症反应的分子生物学机制。方法将24只雄性SD大鼠随机分配至空白组,模型组及电针组,每组8只。空白组SD大鼠喂以12 w的普通饲料,模型组、电针组SD大鼠喂以12 w的D12492高脂饲料。电针组针刺双侧内关、三阴交、足三里及肾俞,1次/d,20 min/次,持续4 w。模型组及空白组不给予电针处理。治疗结束后,禁食12 h,检测葡萄糖输注率(GIR),眼眶静脉窦采血检测各组大鼠空腹血糖(FPG)、空腹胰岛素(FINS)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6等指标含量,使用Western印迹分析血管内皮中核因子(NF)-κB p65表达水平,并于电镜下观察血管内皮超微结构变化。结果治疗后,与空白组比较,模型组大鼠血清FPG、FINS、TNF-α、IL-6水平显著升高(P<0.01),GIR水平明显降低(P<0.01);与模型组比较,电针组大鼠血清FPG、FINS、TNF-α、IL-6水平显著降低,GIR水平明显升高(P<0.01)。与空白组比较,模型组大鼠血管内皮的NF-κB p65磷酸化水平及蛋白表达显著升高(P<0.01);电针组大鼠血管内皮NF-κB p65磷酸化水平及蛋白表达较模型组显著降低(P<0.01)。电针组中大鼠的内皮细胞与壁间隙稍增宽,部分线粒体形态改变,嵴部局部消失。结论电针可通过改善炎症反应而发挥防治IR的作用,其机制可能与调节NF-κB信号转导通路有关。