摘要
目的:探讨吡格列酮(Pio)对游离脂肪酸诱导的胰岛素抵抗大鼠糖代谢和PPAR-γ表达的影响。方法:采用扩展正糖钳夹实验和[3-3H]标记葡萄糖示踪技术,观察了4h脂质灌注导致大鼠血浆游离脂肪酸(FFA)升高引起糖代谢和脂肪组织PPAR-γ表达变化及Pio处理后的影响。结果:在钳夹稳态期,对照组(N组)血浆FFA水平明显降低,而脂质灌注组(L组)和吡格列酮+脂质组(P/L组)FFA水平明显升高。P/L组葡萄糖输注率(GIR)较N组明显降低(P<0.01),而L组又明显低于P/L组(P<0.01);N组和P/L组肝糖输出(HGP)与基础值相比被明显抑制达85%(均P<0.01),在L组,胰岛素对HGP的抑制作用受到明显障碍(仅抑制8.7%)。L组和P/L组葡萄糖清除率(GRd)明显低于N组(P<0.01)。P/L组脂肪组织PPAR-γ表达明显增加。结论:脂质灌注诱导了大鼠胰岛素抵抗。吡格列酮干预使大鼠脂肪组织PPAR-γ表达明显增加,并抑制了内源性肝糖产生,从而部分逆转了脂质诱导的胰岛素抵抗。
AIM： To investigate the effect of pioglitazone （Pio） on glucose metabolism and peroxisome proliferators -activated receptor （PPAR） -γ expression in free fatty acid （FFA） -induced insulin resistance in rats. METH- ODS： A hyperinsulinaemic -euglycaemic clamp and [ 3 -3H ] -glucose tracing technique were used in awake rats. Glucose metabolism in vivo and PPAR -γ in adipose tissue expression were assessed with elevation FFA by lipid infusion over 4 h in rats pretreated with or without Pio. RESULTS： During steady - state of clamp, there was a significant increase in plasma FFA in two lipid -infused groups, compared to control rats （P 〈 0. 01 ）. The glucose infusion rates （GIR） in Pio - treated rats （ P/L group ）, compared with controls, were significantly reduced [ （ 20. 6± 0. 4 ） mg· kg^- 1·min^- 1 vs （33.6 ±0. 6）mg· kg^- 1·min^- 1, P 〈0. 01 ], whereas the GIR was lower in the lipid group （L group） than that in the P/L group[ （ 12. 6 ±0. 8） mg· kg^- 1·min^- 1 vs （20. 6 ±0.4）mg· kg^- 1·min^- 1, P 〈0. 01 ]. The hepatic glucose pro- duction （HGP） was significantly suppressed （ 85 % ） [ （ 18.3± 2. 1 ） mg· kg^- 1·min^- 1 （ basal ） vs （ 2.7± 2.4 ） mg· kg^- 1·min^- 1, and （17.5＋2.6） mg. kg-1 .min-tvs （2.6±1.0）mg· kg^- 1·min^- 1], allP〈0.01 during clamp in control and P/L groups. The suppressive effect of insulin on HGP was significantly blunted in L group[ （17. 3 ±2. 1 ）mg· kg^- 1·min^- 1 vs （ 15.8 ＋ 1.5 ） mg · kg^-1·min^- 1 ]. The rate of glucose disappearance （GRd） was significantly reduced in two lipid - infused rats compared with controls[ （26. 6 ＋ 1.6） mg ·kg^-1· min^-1 and （23. 2±0.9） mg· kg^-1· min -1 vs （37.7±2. 6） nag· kg^-1· min^-1 ,p 〈0. 01 ]. The PPAR -γ expression of adipose tissue in P/L group was significantly upregulated. CONCLUSION： Lipid -infusion induces an acute insulin -resistance in vivo. Pio treatment upregulates the PPAR -γ of adipose tissue and suppresses HGP. Pio can protect partly against lipid - induced insulin resistance.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第7期1399-1403,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30771037
No.30370671)
国家教委春晖计划资助项目(No.2003-56)
重庆市科委应用基础研究基金资助项目(No.02-34)
美国NIH基金资助项目(No.R01-DK58895
toG.B.)
