脂联素受体在胰岛细胞表达,脂联素促进胰岛素的分泌

目的　检测脂联素受体(AR)在大鼠胰岛细胞的表达和脂联素对体外胰岛细胞分泌胰岛素的影响。方法　RT PCR和免疫细胞化学方法检测AR1、AR2的mRNA和蛋白表达;并在体外用脂联素(100μg/L)和不同浓度葡萄糖(3. 3, 5. 6, 16. 7mmol/L)处理胰岛细胞,放免法测定上清液的胰岛素浓度。结果　RT PCR扩增出胰岛AR1和AR2基因,并经直接和亚克隆测序证实;胰岛免疫细胞化学荧光染色AR1和AR2呈阳性;经脂联素处理后的胰岛细胞,在高糖(16. 7mmol/)培养 6~24h,其胰岛素分泌持续增加(均P<0. 05)。结论　胰岛细胞上存在AR1和AR2,以前者为主。在高糖情况下,一定浓度的脂联素可在体外促进胰岛细胞的胰岛素分泌和释放。     

脂联素对刀豆球蛋白A诱导小鼠免疫性肝损伤的保护作用

目的探讨脂联素(ADPN)是否对肝脏的免疫性损伤具有保护作用以及可能的作用机制。方法将小鼠ADPN基因高效表达载体导入小鼠体内,获得高血清ADPN模型小鼠(表达载体组),与导入空载体的对照小鼠(空载体组)同时静脉内注射刀豆球蛋白A(Con A),以诱导肝脏的免疫性损伤,测定不同时间点血清ALT浓度,并进行肝组织病理学检查(HE染色),观察两组小鼠肝脏损伤程度是否有差异。比较两组间血清TNFα浓度的不同,探讨可能的作用机制。结果表达载体组小鼠注射Con A后血清ALT水平的升高明显低于空载体组,差异有统计学意义(P<0.01),组织学检查也显示表达载体组小鼠的肝损伤明显低于空载体组。经统计分析表明,ALT水平与血清ADPN水平成负相关(r=-0.5034,P=0.0121)。表达组小鼠血清TNFα水平明显低于空载体组(P<0.01)。结论脂联素对Con A诱导的肝脏免疫性损伤具有保护作用,其作用机制可能与抑制TNFα的产生进而阻断肝细胞遭受免疫性攻击有关。     

Blood glucose lowering by means of lifestyle intervention has different effects on adipokines as compared with insulin treatment in subjects with type 2 diabetes

Aims/hypothesis Adipokines may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature. We studied the effect of different glucose-lowering therapies on serum levels of plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), TNF-α, leptin, adiponectin and ghrelin in patients with type 2 diabetes.Subjects and methods Twenty-eight patients with poorly controlled type 2 diabetes who were receiving oral hypoglycaemic agents were allocated to one of the following groups, and treated for 1 year: (1) lifestyle intervention (L); (2) insulin treatment (I); and (3) combined treatment (L+I).Results Similar improvements in glycaemic control occurred in all three groups. There was a reduction in body weight of 3.0 kg (median) (95% CI −5.9 to −2.0) in group L, whereas in groups L+I and I body weight increased by 3.5 kg (95% CI 1.5–4.9) and 4.9 kg (95% CI −3.1 to 8.2), respectively. By trend analyses, group L had reduced levels of PAI-1 (p=0.002), hs-CRP (p<0.0001) and TNF-α (p=0.006), while no significant changes were observed in the levels of leptin or adiponectin. In group I, the median levels of PAI-1 (p=0.008), TNF-α (p=0.058) and leptin (p=0.004) increased. In the L+I group there was a reduction in PAI-1 levels (p=0.014) and an increase in levels of leptin (p<0.001). The differences in changes in the levels of PAI-1, hs-CRP, TNF-α and leptin between groups were also significant (all p<0.01).Conclusions/interpretation Improvement of glycaemic control through lifestyle intervention in type 2 diabetes had more beneficial effects on adipokine levels than when the same lowering of HbA_1c was achieved with insulin treatment.Electronic Supplementary Material Supplementary material on this article is available at     

氯沙坦对非糖尿病维持性血液透析患者血清脂联素及胰岛素抵抗的影响

目的 探讨氯沙坦对非糖尿病维持性血液透析患者血清脂联素水平和胰岛素抵抗的影响,及非糖尿病维持性血液透析患者血清脂联素与胰岛素抵抗的相关性.方法 测定62例非糖尿病维持性血液透析患者和30名健康对照者的血清胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、白蛋白、尿素氮、肌酐、C反应蛋白、收缩压、舒张压、血清脂联素、血糖、胰岛素,并计算稳态模型胰岛素抵抗指数及胰岛素敏感指数.分析血清脂联素与胰岛素抵抗等指标的相关性.将维持性血液透析患者按随机数字表法分为氯沙坦组(31例)和非氯沙坦组(31例),氯沙坦组给予口服氯沙坦每天50～100 mg,共6个月,测定治疗前、后两组血清脂联素、血糖、胰岛素及计算稳态模型胰岛素抵抗指数及胰岛素敏感指数.结果 维持性血液透析组患者甘油三酯、尿素氮、肌酐、C反应蛋白、血清脂联素、胰岛素、胰岛素抵抗指数、收缩压、舒张压水平与健康对照组比较差异有统计学意义(P分别＜ 0.01,＜0.05);而维持性血液透析组患者高密度脂蛋白及白蛋白水平与健康对照组比较差异也有统计学意义(P＜0.05).氯沙坦治疗组患者血清脂联素和胰岛素抵抗较治疗前比较差异也有统计学意义(P均＜ 0.01).相关分析显示血清脂联素、胰岛素、胰岛素抵抗指数、C反应蛋白、甘油三酯呈负相关(r分别为-0.282,- 0.362,- 0.411,-0.307,P分别＜0.05,＜0.01),血清脂联素与胰岛素敏感指数、胆固醇、高密度脂蛋白呈显著正相关(r分别为0.61、0.249、0.396,P分别＜0.05,＜0.01).结论 氯沙坦可使非糖尿病维持性血液透析患者血清脂联素升高,并减轻维持性血液透析患者高胰岛素血症和胰岛素抵抗.     

原发性高血压患者血清脂联素水平的变化及其与颈动脉内膜中层厚度的关系

目的 探讨血清脂联素在原发性高血压(EH)发病中的作用及与颈动脉内膜中层厚度(IMT)的关系.方法 60例EH患者(EH组)和30例健康体检者(对照组)为研究对象,60例EH组患者根据《中国高血压防治指南(2005年)》中血压的分级标准分为三个亚组,1级EH组、2级EH组、3级EH组,每组20例.采用双抗体夹心ABC-酶联免疫吸附试验(ELISA)法检测血清脂联素水平,采用全自动生化仪测定血脂水平,采用彩色多普勒超声仪测定颈动脉IMT.结果 与对照组比较,EH组及1、2、3级EH组血清脂联素水平降低[(3.94±1.28)、(5.25±1.69)、(4.01±1.27)、(2.56±0.87)mg/L比(7.63±2.50) mg/L],颈动脉IMT增加[(1.30±0.42)、(0.94±0.30)、(1.32±0.44)、(1.65±0.51)mm比(0.69±0.22) mm],差异均有统计学意义(P＜0.05);且EH各亚组间两两比较,随着血压水平升高,血清脂联素水平逐渐降低,颈动脉IMT逐渐增加,差异均有统计学意义(P＜0.05).与对照组比较,EH组及1、2、3级EH组血清TC、TG、LDL-C水平上升[TC:(6.53±2.09)、(5.14±1.66)、(6.59±2.20)、(7.86±2.42) mmol/L比(4.17±1.32)mmol/L;TG:(2.15±0.69)、(1.72±0.55)、(2.07±0.69)、(2.65±0.82) mmol/L比(1.38±0.44) mmol/L; LDL-C:(3.78±1.21)、(3.12±1.01)、(3.74±1.25)、(4.48±1.38)mmol/L比(2.46 ±0.78) mmol/L],HDL-C水平下降[(0.96±0.31)、(1.39±0.45)、(0.85±0.28)、(0.64 ±0.20) mmol/L比(1.69±0.54) mmol/L],差异均有统计学意义(P＜0.05);且EH各亚组间两两比较,随着血压水平升高,血清TC、TG、LDL-C水平上升,HDL-C水平下降,差异均有统计学意义(P＜0.05).血清脂联素水平与颈动脉IMT呈显著负相关(r=-0.435,P＜0.01),与血脂(TC、TG、LDL-C、HDL-C)水平有相关性(P＜0.01).结论 脂联素在EH的发生和发展过程中起着重要作用,并与颈动脉IMT的增厚和血脂代谢紊乱密切相关,顽固性EH患者增加降血脂药物可能会提高降血压治疗的疗效.     

老年高血压和代谢综合征血清脂联素水平变化及其意义

目的:探讨老年高血压和代谢综合症患者血清脂联素水平变化及其意义。方法:60例老年高血压患者、62例老年代谢综合症患者和30例正常老年对照者,检测血压、体重、身高、腰围、空腹血糖、胰岛素、游离脂肪酸、血清脂联素、高敏C反应蛋白、尿素氮、肌酐,计算体重指数,测尿微量蛋白。结果:(1)高血压组和代谢综合症组脂联素水平明显低于正常对照组(P<0.05),体重指数、腹围、尿微量蛋白、游离脂肪酸、血糖、胰岛素、肌酐水平均高于对照组(P<0.05);(2)直线相关分析表明,血清脂联素水平与血压、尿微量蛋白、体重指数、腰围均成负相关(r=-0.230~-0.304,P<0.05~<0.01)。结论:代谢综合症和单纯高血压老年患者脂联素水平降低,且脂联素水平与血压、BMI、腰围及尿微量蛋白呈负相关。     

Adiponectin and the cardiovascular system: from risk to disease

Adiponectin is known to play a role in fatty acid and glucose metabolism through a change in insulin sensitivity and activation of fuel oxidation by AMP-activated protein kinase. Adiponectin can be considered an important factor able to modulate the adipovascular axis which, through genomic and environmental influences, affects the cardiovascular risk milieu, from the pre-metabolic syndrome — through the metabolic syndrome — to the overt atherosclerotic process and its clinical manifestations. Hypoadiponectinaemia can be viewed as an early sign of a complex cardiovascular risk factor predisposing to the atherosclerosis process as well as a contributing factor accelerating the progress of the atherosclerotic plaque. In addition, adiponectin per se holds a protective role thanks to its anti-inflammatory and antiatherogenic properties. The early identification of patients “at cardiovascular risk” means in the current practice to search for indexes of metabolic derangements and pro-inflammatory status (adiponectin) from adolescence and childhood.     

Measurement of salivary adiponectin levels

Abstract We designed a method for measuring salivary adiponectin. In 188 healthy males, salivary adiponectin levels were measured using a commercial enzyme immunoassay kit for plasma with minor modifications. Intra- and inter-assay coefficients of variation for salivary adiponectin ranged from 0.6 to 4.9 and 1.1 to 9.8%, respectively. Salivary adiponectin levels ranged from 0.37 to 6.42 ng/ml, exceeding the kit's detection limit. For the over-43 age group, there was a significant correlation between plasma and salivary adiponectin levels (p<0.000001). These findings suggest the possibilities of salivary adiponectin as a marker of increased risk of non-insulindependent diabetes mellitus or cardiovascular disease.     

上海地区汉族健康人群血清脂联素水平分析

目的探讨上海地区汉族健康人群血清脂联素水平，分析其与年龄、性别、血脂浓度及胰岛素抵抗指数的关系。方法收集400名汉族健康体检者的血清标本，采用酶联免疫吸附双抗夹心（ELISA）法测定血清脂联素水平和血清空腹胰岛素（FINS）水平。结果上海地区汉族健康人血清空腹脂联素水平为（9．48±4．86）μg／ml，各年龄组间比较差异无统计学意义；男性脂联素浓度为（8．46±3．97）μg／ml，女性为（10．22±5．30）μg／ml，男性和女性相比脂联素浓度差异有统计学意义；女性绝经前后脂联素浓度分别为（11．89±4．78）μg／ml和（8．78±4．65）μg／ml，两者脂联素浓度差异有统计学意义。结论①血清脂联素浓度在各年龄段差异无统计学意义；女性脂联素浓度高于男性，差别有统计学意义（P〈0．05）；绝经前、后女性脂联素浓度差异有统计学意义（P〈0．05）。②血清脂联素水平与空腹胰岛素水平、体重、体重指数、腰臀比、收缩压、LDL—C等指标呈负相关，与HDL—C水平呈正相关。     

The development of microalbuminuria is associated with raised longitudinal adiponectin levels in female but not male adolescent patients with type 1 diabetes

AIMS/HYPOTHESIS: We determined the longitudinal relationship between adiponectin levels and the development of microalbuminuria in an inception cohort of children with type 1 diabetes. METHODS: Blood samples collected annually over a median of 9.0 (range 1.3-14.9) years were assayed for adiponectin and HbA(1c) in 55 children (36 girls) with type 1 diabetes and microalbuminuria whose age of onset of diabetes was 9.4 years (range 2.2-15.4). Samples were also assayed from normoalbuminuric children (controls) matched for age, sex and duration of diabetes. RESULTS: Overall, adiponectin levels were higher in girls than in boys, but only after 11 years of age (median [range]: 15.3 [5.8-124.4] vs 11.6 [4.1-26.5] mg/l, p < 0.001). Furthermore, adiponectin levels were higher in girls with microalbuminuria than in control girls, but this was only apparent after the onset of microalbuminuria (p = 0.001, adjusted for BMI, daily insulin dose, HbA(1c) and age). In boys, adiponectin levels did not differ between those with microalbuminuria and controls. Further sex-related discordant associations with adiponectin levels were observed; in girls, adiponectin levels were positively related to HbA(1c) levels (r = 0.2, p = 0.05) and urine albumin excretion (r = 0.3, p < 0.05) and inversely related to BMI (r = -0.2, p < 0.05). These associations were absent in boys. CONCLUSIONS/INTERPRETATION: In adolescent girls with type 1 diabetes but not in boys, adiponectin levels increase with increasing urine albumin excretion and onset of microalbuminuria. Although causal links cannot be inferred, this sexual dimorphism may reflect interactive effects of hyperglycaemia and sex steroids on risk of complications and adiponectin production.