Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess
Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess
复制标题
DOI：
10.1152/ajpendo.00663.2011
复制
发表时间：
2012-10-01
影响因子：
5.1
通讯作者：
Garvey, W. Timothy
中科院分区：
文献类型：
--
作者：
Liu, Jiarong;Zhang, Wei;Garvey, W. Timothy
刘J，张文，庄GC，希尔HS，田L，傅Y，Moellering DR，Garvey WT。 TRIB3 在短期禁食和营养过剩期间调节胰岛素敏感性和营养代谢中的作用。 Am J Physiol Endocrinol Metab 303：E908-E916，2012。首次发表于 2012 年 7 月 31 日； doi:10.1152/ajpendo.00663.2011.-我们之前已经提出，Tribbles 同源物 3 (TRIB3) 是胰岛素敏感组织中 Akt 活性的负调节因子，可以在慢性高血糖条件下介导葡萄糖诱导的肌肉胰岛素抵抗（Liu J、Wu X、Franklin JL、Messina JL、Hill HS、Moellering DR、Walton RG，马丁·M，加维·WT。 Am J Physiol Endocrinol Metab 298：E565-E576，2010）。在当前的研究中，我们评估了营养过剩和禁食对骨骼肌和脂肪组织中 TRIB3 的短期生理调节，以及 TRIB3 调节葡萄糖转运和线粒体氧化的能力。在 Sprague-Dawley 大鼠中，我们发现与对照组相比，短期禁食增强了胰岛素敏感性，同时肌肉中 TRIB3 mRNA（66%，P < 0.05）和蛋白质（81%，P < 0.05）减少，脂肪组织中 TRIB3 mRNA（96%，P < 0.05）和蛋白质（接近 10 倍，P < 0.05）增加。非禁食对照。另一方面，喂食西方饮食7天的大鼠出现胰岛素抵抗，同时肌肉中TRIB3 mRNA（155%，P < 0.05）和蛋白质（69%，P = 0.0567）增加，脂肪中mRNA（76%，P < 0.05）和蛋白质（70%，P < 0.05）减少。在使用骨骼肌细胞进行的葡萄糖转运和线粒体氧化研究中，我们发现稳定的 TRIB3 过表达会损害胰岛素刺激的葡萄糖摄取，而不影响基础葡萄糖转运，并增加基础葡萄糖氧化和最大解偶联耗氧率。随着TRIB3的稳定敲低，基础和胰岛素刺激的葡萄糖转运率增加，而基础葡萄糖氧化和最大解偶联耗氧率降低。总之，TRIB3 根据营养可用性水平对肌肉和脂肪中的葡萄糖摄取和氧化产生相反的影响。上述数据首次表明 TRIB3 在营养缺乏和过量条件下作为胰岛素敏感性和线粒体葡萄糖氧化的有效生理调节剂。
Liu J, Zhang W, Chuang GC, Hill HS, Tian L, Fu Y, Moellering DR, Garvey WT. Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess. Am J Physiol Endocrinol Metab 303: E908-E916, 2012. First published July 31, 2012; doi:10.1152/ajpendo.00663.2011.-We have suggested previously that Tribbles homolog 3 (TRIB3), a negative regulator of Akt activity in insulin-sensitive tissues, could mediate glucose-induced insulin resistance in muscle under conditions of chronic hyperglycemia (Liu J, Wu X, Franklin JL, Messina JL, Hill HS, Moellering DR, Walton RG, Martin M, Garvey WT. Am J Physiol Endocrinol Metab 298: E565-E576, 2010). In the current study, we have assessed short-term physiological regulation of TRIB3 in skeletal muscle and adipose tissues by nutrient excess and fasting as well as TRIB3's ability to modulate glucose transport and mitochondrial oxidation. In Sprague-Dawley rats, we found that short-term fasting enhanced insulin sensitivity concomitantly with decrements in TRIB3 mRNA (66%, P < 0.05) and protein (81%, P < 0.05) in muscle and increments in TRIB3 mRNA (96%, P < 0.05) and protein (similar to 10-fold, P < 0.05) in adipose tissue compared with nonfasted controls. On the other hand, rats fed a Western diet for 7 days became insulin resistant concomitantly with increments in TRIB3 mRNA (155%, P < 0.05) and protein (69%, P = 0.0567) in muscle and a decrease in the mRNA (76%, P < 0.05) and protein (70%, P < 0.05) in adipose. In glucose transport and mitochondria oxidation studies using skeletal muscle cells, we found that stable TRIB3 overexpression impaired insulin-stimulated glucose uptake without affecting basal glucose transport and increased both basal glucose oxidation and the maximal uncoupled oxygen consumption rate. With stable knockdown of TRIB3, basal and insulin-stimulated glucose transport rates were increased, whereas basal glucose oxidation and the maximal uncoupled oxygen consumption rate were decreased. In conclusion, TRIB3 impacts glucose uptake and oxidation oppositely in muscle and fat according to levels of nutrient availability. The above data for the first time implicate TRIB3 as a potent physiological regulator of insulin sensitivity and mitochondrial glucose oxidation under conditions of nutrient deprivation and excess.