吡格列酮对脂质诱导胰岛素抵抗大鼠的影响及其机制研究  

Effects of pioglitazone on lipid-induced insulin resistance in rats

作　　者：杨刚毅[1] 张凌[1] 李伶[2] 唐毅 李清明[4] 方超[1] 孙勤[1] 李钶[1] 舒朝忠[2] Gunther Boden 

机构地区：[1]重庆医科大学附属第二医院内分泌科,400010 [2]重庆医科大学附属第二医院检验系临床生化教研室,400010 [3]Cencotor公司肿瘤研究室 [4]重庆医科大学附属第二医院 检验系临床生化教研室,400010 [5]Temple大学医学院附属医院一般临床研究中心

出　　处：《中华内分泌代谢杂志》2006年第3期273-276,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(30270631和30370671);国家教委春晖计划基金项目(2003-56);美国NIH基金(R01-DK 58895;to G.B)

摘　　要：目的探讨吡格列酮(Pio)对脂质诱导的胰岛素抵抗(IR)大鼠糖代谢、血浆脂联素和抵抗素浓度及组织抵抗素水平的影响。方法采用清醒状态大鼠进行扩展高胰岛素-正糖钳夹术,检测4h脂质灌注升高血浆游离脂肪酸(FFA)引起的IR状态下,肝糖及外周组织糖代谢,血浆脂联素和抵抗素浓度,肝、肌肉、脂肪组织抵抗素水平的变化,以及经Pio处理后的影响。结果在钳夹稳态期,脂质灌注组(L组)和Pio处理+脂质灌注组(P/L组)FFA水平明显较对照组升高。P/L组葡萄糖输注率(GIR)较对照组降低[(20.6±0.9vs 33.6±1.5)mg·kg^(-1)·min^(-1),JP＜0.01],而L组又低于P/L组[(12.6±1.7)vs (20.6±0.9)mg·kg^(-1)·min^(-1),P＜0.01]；对照组和P/L组肝糖输出(HGP)与基础值相比被抑制85%,在L组胰岛素对HGP的抑制作用明显障碍。L组和P/L组葡萄糖清除率(G_(Rd))低于对照组(P＜0.01)。P/L组基础血浆抵抗素水平低于对照组[(7.8±1.3vs 29.1±3.1)μL,P＜0.01]。脂质灌注后P/L组抵抗素浓度明显升高,但仍低于L组[(18.1±3.8vs 47.0±2.2)μg/L,P＜0.01]。P/L组基础血浆脂联素水平明显高于对照组和L组[(3.9±0.2vs 2.8±0.1和2.6±0.2)mg/L,P＜0.01]。但在钳夹结束后,L和P/L组血浆脂联素水平降低(均P＜0.05)。P/L组肝脏抵抗素水平低于对照组和L组(均P＜0.05)；L组骨骼肌抵抗素水平高于对照组和P/L组(均P＜0.05)；各组脂肪组织抵抗素水平差异无统计学意义。结论脂质灌注在体内诱导了一种急性IR。Pio干预部分阻断了脂质诱导的IR。抵抗素和脂联素的变化在IR的发生和发展中可能发挥了一定的作用。Objective To investigate the effects of pioglitasone on glucose metabolism, circulating resistin and ediponectin concentrations, and tissue resistin levels in rats with insulin resistance induced by free fatty acid （FFA）. Methods A hyperinsulinaemie-euglycaemic clamp and [ 3-^3H ]-glucose tracing technique were used in awake rats. Insulin-mediated peripheral and hepatic glucose metabolism, plasma resistin and adiponectin levels, resistin levels in tissues were assessed by hyperinsulinaemic-euglyeacmic clamp with elevation of FFA by lipid infusion over 4 h in rats pretreated with or without pioglitazone. Results During steady-state of clamp, there was a significant increase in plasma FFA in lipid-infused group （ L group） and pioglitazone-pretreated lipid-infused group （ P/L group） compared to control rats （ P 〈 0.01 ）. The glucose infusion rate （GIR） in P/L group was significantly reduced as compared with controls [ （ 20.6 ± 0.9 vs 33.6 ± 1.5 ）mg · kg^-1·min^- 1, p 〈 0. 01 ], whereas the GIR was lower in L group than in P/L group [ （ 12.6 ± 0.8 vs 20.6 ± 0.9 ） mg · kg^-1·min^- 1, p 〈 0.01 ]. As compared with baseline, the hepatic glucose production （HGP） was significantly suppressed by 85% [（18.3±2.1vs2.7±2.4）mg· kg^-1·min^- 1 and （17.5±2.6vs2.6±1.0）mg· kg^-1·min^- 1, both P〈 0.01 ] during the hyperinsulinaemie clamp in control and P/L groups. The suppressive effect of insulin on HGP was significantly blunted in L group [（17. 3 ±2. 1 vs 15. 8 ± 1.5]mg · kg^-1·min^- 1. The rate of glucose disappearance （Gad） was reduced in L group and P/L group compared with controls （P 〈 0.01 ）. Baseline plasma resistin level was lower in P/L group than that in the controls [ （7.8 ± 1.3 vs 29.1 ± 3.1 ） μg/L, P 〈 0.01 ]. After lipid infusion, plasma resistin levels significantly increased in P/L group, but remained lower than that of L group [ （ 18.1 ± 3.8 vs 47.0 ± 2.2 ） μg/L, P 〈 0.01 ]. Baseline adiponectin level was higher in P/L g

关 键 词：胰岛素抵抗 吡格列酮 脂质 脂联素 抵抗素 

分 类 号：R587.1[医药卫生—内分泌]