Altered triglyceride-rich lipoprotein production in Zucker diabetic fatty rats
Altered triglyceride-rich lipoprotein production in Zucker diabetic fatty rats
复制标题
DOI：
10.1152/ajpendo.00297.2003
复制
发表时间：
2004-07-01
影响因子：
5.1
通讯作者：
Sparks, CE
中科院分区：
文献类型：
--
作者：
Chirieac, DV;Collins, HL;Sparks, CE
在 Zucker 糖尿病脂肪 (ZDF) 大鼠（胰岛素抵抗 2 型糖尿病进展模型）中研究了富含甘油三酯的脂蛋白 (TRL) 的产生。通过用 Triton WR-1339 阻断分解代谢来测量体内 TRL 的产生。十周 ZDF 大鼠出现高胰岛素血症，TRL 产生增加 [甘油三酯和载脂蛋白 B (apoB)]。二十周的 ZDF 大鼠胰岛素缺乏，TRL 产生与瘦对照相似。胰岛素输注可抑制 10 周和 20 周 ZDF 大鼠的葡萄糖和游离脂肪酸。在 10 周的大鼠中，胰岛素不会减少 TRL 产生的增加；然而，在第 20 周，TRL 的产生受到胰岛素的抑制。对来自 10 周 ZDF 大鼠的肝细胞进行的体外研究表明，与来自 20 周 ZDF 和对照瘦大鼠的肝细胞的反应和敏感性相比，胰岛素剂量对 apoB 分泌的影响最小。肝甾醇调节结合蛋白 (SREBP)-1c mRNA 水平在 10 周时增加，但在 20 周时恢复到对照水平。 10 周和 20 周时，ApoB mRNA 水平与瘦对照相似。与高胰岛素血症相关的高甘油三酯血症有以下两种机制：TRL 合成增加和 TRL 抑制丧失。高胰岛素血症大鼠中甘油三酯产量的增加可能与 SREBP-1c 表达的增加有关，而 apoB 产量的增加涉及转录后过程。
Triglyceride-rich lipoprotein (TRL) production was studied in Zucker diabetic fatty (ZDF) rats, a model of insulin-resistant type 2 diabetes progression. TRL production was measured in vivo by blocking catabolism with Triton WR-1339. Ten-week ZDF rats are hyperinsulinemic with increased TRL production [both triglyceride and apolipoprotein B (apoB)]. Twenty-week ZDF rats are insulinopenic, and TRL production is similar to lean controls. Insulin infusion suppresses glucose and free fatty acids in 10- and 20-wk ZDF rats. Increased TRL production is not reduced by insulin in 10-wk rats; however, at 20 wk, TRL production is suppressed by insulin. In vitro studies with hepatocytes derived from 10- wk ZDF rats showed minimal insulin dose effects on apoB secretion compared with the response and sensitivity of hepatocytes derived from 20-wk ZDF and control lean rats. Hepatic sterol regulatory-binding protein (SREBP)-1c mRNA levels are increased at 10 wk but return to control levels at 20 wk. ApoB mRNA levels are similar to lean controls at 10 and 20 wk. The following two mechanisms for hypertriglyceridemia associated with hyperinsulinemia are suggested: increased TRL synthesis and loss of TRL suppression. Increased triglyceride production in hyperinsulinemic rats likely relates to increased expression of SREBP-1c, whereas increased apoB production involves posttranscriptional processes.