Li Ling, Yang Gang-yi
Department of Clinic Biochemistry, Chongqing Medical University, Chongqing 400016, China.
Zhonghua Yi Xue Za Zhi. 2004 Oct 2;84(19):1645-8.
To investigate the effect of free fatty acid-induced insulin resistance on plasma ghrelin level.
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.
120 minutes after the beginning of hyperinsulinaemic-euglycaemic clamping the plasma FFA was significant increased from 742 micromol/L +/- 51 micromol/L to 2346 micromol/L +/- 238 micromol/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).
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.
探讨游离脂肪酸诱导的胰岛素抵抗对血浆胃饥饿素水平的影响。
将24只雄性SD大鼠经右颈静脉插入静脉导管至右心房，经左颈动脉插入动脉导管。至少5天后，大鼠在禁食12 - 14小时后进行胰腺钳夹。然后将大鼠分为2组：脂质输注组（在钳夹期间通过动脉导管输注脂质/肝素4小时，钳夹开始60分钟后经静脉导管输注Ci 3 - 3H -葡萄糖直至钳夹结束，钳夹开始120分钟后输注胰岛素和25%葡萄糖2小时，使血糖维持在约5 mmol/L）和对照组（输注生理盐水）。钳夹前后采集静脉血检测胃饥饿素浓度。在0、120、200、230和240分钟时间点采集血浆标本检测血糖、胰岛素、游离脂肪酸和3 - 3H葡萄糖活性浓度。
脂质输注组在高胰岛素 - 正常血糖钳夹开始120分钟后，血浆游离脂肪酸从742 μmol/L±51 μmol/L显著升高至2346 μmol/L±238 μmol/L（P < 0.01）。与对照组相比，脂质输注大鼠的葡萄糖输注率（GIR）显著降低35%（钳夹200 - 240分钟后，平均值为12.6 mg·kg⁻¹·min⁻¹±1.5 mg·kg⁻¹·min⁻¹对34.0 mg·kg⁻¹·min⁻¹±1.6 mg·kg⁻¹·min⁻¹，P < 0.01）。钳夹结束时（240分钟后），脂质输注组的GIR为12.0 mg·kg⁻¹·min⁻¹±1.9 mg·kg⁻¹·min⁻¹，显著低于对照组（34.7 mg·kg⁻¹·min⁻¹±1.7 mg·kg⁻¹·min⁻¹，P < 0.01）。钳夹结束时，对照组大鼠的肝葡萄糖生成（HGP）显著抑制88%（从19.0 mg·kg⁻¹·min⁻¹±4.5 mg·kg⁻¹·min⁻¹降至2.3 mg·kg⁻¹·min⁻¹±0.9 mg·kg⁻¹·min⁻¹，P < 0.01）。脂质输注大鼠中胰岛素对HGP的抑制作用显著减弱（200 - 240分钟：从18.7 mg·kg⁻¹·min⁻¹±3.0 mg·kg⁻¹·min⁻¹升至23.2 mg·kg⁻¹·min⁻¹±3.1 mg·kg⁻¹·min⁻¹，P < 0.05）。正常血糖 - 高胰岛素钳夹结束时，对照组血浆胃饥饿素水平与基础水平相比显著降低（584 ng/L±67 ng/L对892 ng/L±90 ng/L，P < 0.05）。脂质输注4小时也使血浆胃饥饿素浓度与基础水平相比显著降低（548 ng/L±82 ng/L对936 ng/L±78 ng/L，P < 0.05）。正常血糖 - 高胰岛素钳夹结束时，对照组和脂质输注组大鼠的血浆胃饥饿素水平无显著差异（584 ng/L±67 ng/L对548 ng/L±82 ng/L，P > 0.05）。Pearson分析显示，空腹血浆胃饥饿素浓度与空腹血浆胰岛素水平呈负相关（r = - 0.52，P < 0.05），与血糖呈负相关（r = - 0.61，P < 0.05）。
脂质输注损害胰岛素抑制脂肪分解和肝葡萄糖输出的能力，以及胰岛素介导的外周组织葡萄糖利用。正常血糖 - 高胰岛素钳夹降低大鼠循环胃饥饿素水平，但体内脂质输注诱导的急性胰岛素抵抗对循环胃饥饿素水平无影响。
