游离脂肪酸诱导的胰岛素抵抗对血浆ghrelin水平的影响

Effect of free fatty acid-induced insulin resistance on plasma ghrelin level:an experimental study with rats

目的 探讨正糖 高胰岛素钳夹及游离脂肪酸 (FFA)对大鼠血浆ghrelin浓度的影响。方法 建立清醒状态下大鼠正常血糖 高胰岛素钳夹技术 ,在钳夹前后分别测定大鼠血浆ghrelin浓度 ,脂质灌注组大鼠 12只 ,生理盐水组 12只为对照 ,并用 3 3 H葡萄糖作为示踪剂测定了胰岛素介导的外周和肝糖的代谢。结果 在胰岛素钳夹中 ,脂质灌注组大鼠血浆FFA明显增加 (从 74 2 μmol/L±5 1μmol/L到 2 346 μmol/L± 2 38μmol/L ,P <0 0 1)。脂质灌注组葡萄糖输注率 (GIR)明显低于对照组( 2 0 0 2 4 0min ,平均 12 6mg·kg-1·min-1± 1 5mg·kg-1·min-1vs 34 0mg·kg-1·min-1± 1.6mg·kg-1·min-1,P <0 0 1)。到钳夹结束时 ,下降至相应对照值的 35 % ( 2 4 0min ,12 0mg·kg-1·min-1± 1 9mg·kg-1·min-1vs 34 7mg·kg-1·min-1± 1 7mg·kg-1·min-1,P <0 0 1)。对照组肝糖产率 (HGP)明显被抑制 ( 88% ) ,从 19 0mg·kg-1·min-1± 4 5mg·kg-1·min-1降至 2 3mg·kg-1·min-1± 0 9mg·kg-1·min-1(P <0 0 1)。脂质输注组胰岛素对HGP的抑制作用明显障碍 ( 2 0 0 2 4 0min ,从 18 7mg·kg-1·min-1± 3 0mg·kg-1·min-1到 2 3 2mg·kg-1·min-1± 3 1mg·kg-1·min-1,P <0 0 5 )。钳夹术结束时 。

Objective To investigate the effect of free fatty acid induced insulin resistance on plasma ghrelin level. Methods A venous catheter was inserted through the right jugular vein into the right atrium, and an arterial catheter was inserted through the left carotid in 24 SD rats. After at least 5 days the rats underwent clamping of pancreas after fasting of 12 14 hours. Then the rats were divided into 2 equal groups: lipid infused group (lipid/heparin were infused during the clamping through the arterial catheter for 4 hours, 60 minutes after the beginning of clamping Ci 3 3H glucose was infused through the venous catheter till the end of clamping, 120 minutes after the beginning of clamping insulin and 25% glucose were infused for 2 hours with the blood sugar remaining at about 5 mmol/L) and control group (normal saline were infused). Before and after clamping venous blood was collected to detect the concentration of ghrelin. At the time points 0, 120, 200, 230, and 240 min specimens of plasma were collected to detect the concentrations of blood sugar, insulin, free fatty acid, and 3 3H glucose activity. Results 120 minutes after the beginning of hyperinsulinaemic-euglycaemic clamping the plasma FFA was significant increased from 742 μmol/L±51 μmol/L to 2346 μmol/L±238 μmol/L ( P <0.01) in the lipid infused group. The glucose infusion rate (GIR) in the lipid infused rats, compared to the control rats, was significantly reduced by 35% (200 240 min after, with an average value of 12.6 mg·kg -1 ·min -1 ±1.5 mg·kg -1 ·min -1 vs. 34.0 mg· kg -1 · min -1 ±1.6 mg·kg -1 ·min -1 , P < 0.01). By the end of clamping (240 min after) the GIR in the lipid infused group was 12.0 mg·kg -1 ·min -1 ±1.9 mg· kg -1 ·min -1 , significantly lower than that in the control group (34.7 mg·kg -1 ·min -1 ±1.7 mg·kg -1 ·min -1 , P <0.01). At the end of clamping, the hepatic glucose production (HGP) in the controls rats was significantly suppressed by 88% (from 19.0 mg·kg -1 ·min -1 ±4.5 mg·kg -1 ·min -1 to 2.3 mg· kg -1 ·min -1 ±0.9 mg·kg -1 ·min -1 , P <0 01). The suppressive effect of insulin on HGP was significantly blunted in the lipid infused rats ( 200 240 min: from 18.7 mg·kg -1 ·min -1 ±3.0 mg·kg -1 ·min -1 to 23.2 mg·kg -1 ·min -1 ±3.1 mg·kg -1 ·min -1 , P < 0.05). At the end of euglycemic hyperinsulinemic clamping the plasma ghrelin levels in the controls was significantly decreased as compared with the basal level (584 ng/L±67 ng/L vs. 892 ng/L±90 ng/L, P < 0.05). Lipid infusion of 4 hours also caused a significant decrease in plasma ghrelin concentration in comparison with the basal levels (548 ng/L± 82 ng/L vs. 936 ng/L±78 ng/L, P < 0.05). At the end of euglycemic hyperinsulinemic clamping, there was no significant difference in the plasma ghrelin levels between the control and lipid infused rats (584 ng/L±67 ng/L vs. 548 ng/L±82 ng/L, P >0.05) . Pearson analysis showed that 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 impairs the ability of insulin to suppress lipolysis and hepatic glucose output, as well as insulin mediated glucose utilization in peripheral tissue. Euglycemic hyperinsulinemic clamping decreases the circulating ghrelin level in rats, but an acute insulin resistance induced by lipid infusion in vivo has no effect on circulating ghrelin level.