Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance
Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance
复制标题
DOI：
10.1007/s00125-007-0790-1
复制
发表时间：
2007-11-01
期刊：
影响因子：
8.2
通讯作者：
Boren, J.
中科院分区：
文献类型：
--
作者：
Adiels, M.;Westerbacka, J.;Boren, J.
目的/假设VLDL 1的过度产生似乎是与2型糖尿病相关的血脂异常的中心病理生理学特征。我们探讨了肝脏脂肪与胰岛素抑制VLDL 1生成之间的关系，这些受试者具有广泛的肝脏脂肪含量。方法在20名男性受试者中，在高胰岛素-正常血钳夹期间，使用多室模型测定推注[H-2（3）]亮氨酸和[H-2（5）]甘油后VLDL 1和VLDL 2中载脂蛋白B和TG的动力学参数：8名2型糖尿病患者和12名对照志愿者。参与者被分为两组，肝脏脂肪含量低或高。所有糖尿病患者均在高肝脂group.Results的结果显示，在极低密度脂蛋白1-载脂蛋白B和-三酰甘油分泌的参与者在低肝脂肪胰岛素输注过程中的快速下降。相比之下，高肝脏脂肪的参与者在VLDL 1分泌方面没有显着变化。胰岛素输注后的VLDL 1抑制与NEFA抑制相关，并且胰岛素抑制血浆NEFA的能力在高肝脏脂肪参与者中受损。一个新的发现是一个负向反应VLDL 1和VLDL 2分泌的参与者与低肝脂肪：VLDL 1分泌减少急性胰岛素输注后，而VLDL 2分泌increased.Conclusions/interpretation胰岛素下调VLDL 1分泌，并增加VLDL 2分泌的参与者与低肝脂肪，但未能抑制VLDL 1分泌的参与者与高肝脂肪，导致生产过剩的VLDL 1。因此，肝脏脂肪与缺乏对胰岛素的VLDL 1抑制有关。
Aims/hypothesis Overproduction of VLDL1 seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL1 production by insulin in participants with a broad range of liver fat content.Methods A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL1 and VLDL2 after a bolus of [H-2(3)]leucine and [H-2(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group.Results The results showed a rapid drop in VLDL1-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL1 secretion. The VLDL1 suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL1 and VLDL2 secretion in participants with low liver fat: VLDL1 secretion decreased acutely after insulin infusion whereas VLDL2 secretion increased.Conclusions/interpretation Insulin downregulates VLDL1 secretion and increases VLDL2 secretion in participants with low liver fat but fails to suppress VLDL1 secretion in participants with high liver fat, resulting in overproduction of VLDL1. Thus, liver fat is associated with lack of VLDL1 suppression in response to insulin.