Insulin Promotes Glucose Consumption via Regulation of miR-99a/mTOR/PKM2 Pathway

被引:33
作者
Li, Wei [1 ]
Wang, Jing [1 ]
Chen, Qiu-Dan [1 ]
Qian, Xu [1 ]
Li, Qi [1 ]
Yin, Yu [1 ]
Shi, Zhu-Mei [2 ]
Wang, Lin [1 ]
Lin, Jie [4 ]
Liu, Ling-Zhi [3 ]
Jiang, Bing-Hua [1 ,3 ]
机构
[1] Nanjing Med Univ, Dept Pathol, Ctr Canc, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Nanjing, Jiangsu, Peoples R China
[3] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA
[4] Fujian Normal Univ, Fac Software, Fuzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
PYRUVATE-KINASE M2; HYPOXIA-INDUCIBLE FACTOR-1; FACTOR-I; DIABETES-MELLITUS; MAMMALIAN TARGET; SKELETAL-MUSCLE; METABOLISM; RESISTANCE; MICRORNAS; GROWTH;
D O I
10.1371/journal.pone.0064924
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Insulin is known to regulate multiple cellular functions and is used for the treatment of diabetes. MicroRNAs have been demonstrated to be involved in many human diseases, including Type 2 diabetes. In this study, we showed that insulin decreased miR-99a expression levels, but induced glucose consumption and lactate production, and increased the expression of mTOR, HIF-1 alpha and PKM2 in HepG2 and HL7702 cells. Forced expression of miR-99a or rapamycin treatment blocked insulin-induced PKM2 and HIF-1 alpha expression, and glucose consumption and lactate production. Meanwhile, knockdown of HIF-1 alpha inhibited PKM2 expression and insulin-induced glucose consumption. Taken together, these findings will reveal the role and mechanism ofinsulin in regulating glycolytic activities via miR-99a/mTOR.
引用
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页数:8
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