目的:探讨脂质灌注对大鼠血浆抵抗素和ghrelin的影响。方法:采用正糖钳夹技术,在钳夹前后分别测定生理盐水对照组和脂质灌注组血浆抵抗素和ghrelin浓度,并用[^3H]-葡萄糖作为示踪剂测定外周组织和肝糖的代谢。结果:脂质灌注组大鼠血浆游离脂肪酸(FFA)明显增加(P〈0.01),葡萄糖输注率(GIR)明显降低(P〈0.01)。对照组肝糖产率(HGP)明显被抑制(88%)。脂质输注组胰岛素对HGP的抑制作用明显减弱。在钳夹期间。脂质组与对照组比葡萄糖清除率(GRd)轻度降低。在正糖钳夹术结束时,对照组血浆ghrelin水平与钳夹前相比明显降低(P〈0.05)。4h的脂质灌注也引起了血浆ghrelin浓度的明显下降(P〈0.05),但是在钳夹结束时和对照组比没有明显差异。相关性分析表明空腹血浆ghrelin水平与空腹胰岛素和血糖呈明显负相关(r=-0.52和r=-0.61。P〈0.05)。脂质灌注后大鼠血浆抵抗素水平较灌注前和对照组明显升高(P〈0.01),空腹血浆抵抗素浓度与空腹FFA(r=0.68,P〈0.01)、血糖(r=0.66,P〈0.01)呈明显正相关。结论:脂质灌注诱导了肝脏和外周的胰岛素抵抗,抵抗素在胰岛素抵抗的形成中可能具有重要作用。高胰岛素血症,而不是游离脂肪酸,降低了大鼠循环ghrelin水平。
AIM: To investigate the effects of lipid - induced insulin resistance on plasma resistin and ghrelin levels in awake rats. METHODS: A hyperinsalinaemic- euglycaemic clamp was established in awake chronically catheterized rats. Two groups of rats were studied either with a 4 h intraarterial infusion of lipid/hepafin or saline. Insulin - mediated peripheral and hepatic glucose metabolism was assessed by insulin clamp combined with [^3H] - glucose infusion, and plasma resistin and ghrelin concentrations were examined before and -after clamp with ELISA. RESULTS: During clamp, there was a significant increase in plasma free fatty acid (FFA, P 〈 0.01) and significant decrease in glucose infusion rates (GIR, P 〈 0.01) in lipid - infused group. At the end of clamp study, the hepatic glucose production (HGP) in controls rats was significantly suppressed to - 88%. The suppressive effect of insulin on HGP was significantly blunted in the lipid - infused rats. Plasma resistin levels in the lipid infusion rats were markedly elevated, compared to control rats and before infusion. A lipid infusion of 4 h also caused a significant decrease in plasma ghrelin concentration, when compared to -basal levels. But at the end of clamp, plasma ghrelin levels in control and lipid- infused rats had no difference. Fasting plasma resistin concentrations were correlated with plasma FFA levels ( r = 0.68, P 〈 0.01 ), blood glucose ( r = 0.66, P 〈 0.01 ), and fasting plasma ghrelin concentration was negatively correlated with fasting plasma insulin levels ( r = - 0.52, P 〈 0.05) and blood glucose ( r = - 0.61, P 〈 0.05). CONCLUSION: Lipid - infusion induces a hepatic and peripheral insulin resistance, and circulating resistin is likely to play a major role in insulin resistance. Hyperinsulinemia, but not FFA, decreases circtdating ghrelin in rats.