Decreased carboxylesterases expression and hydrolytic activity in type 2 diabetic mice through Akt/mTOR/HIF-1α/Stra13 pathway

作者：Chen, Ruini; Wang, Yuwen; Ning, Rui; Hu, Jinhua; Liu, Wei; Xiong, Jing; Wu, Lili; Liu, Jie; Hu, Gang; Yang, Jian^*

来源：Xenobiotica, 2015, 45(9): 782-793.

DOI：10.3109/00498254.2015.1020353

• Akt/mTOR/HIF-1 alpha/Stra13 pathway
• carboxylesterase 1d (Ces1d)
• carboxylesterase 1e (Ces1e)
• type 2 diabetes
• insulin

1. This study investigated the alteration of carboxylesterases in type 2 diabetes. We found that the carboxylesterase 1d (Ces1d) and carboxylesterase 1e (Ces1e) expression and the capacity of hydrolytic activity of liver and intestine decreased, whereas the Akt/mTOR/HIF-1 alpha/Stra13 (DEC1) signaling was activated in T2D mice. Consistently, high insulin could give rise to the same results in the high-glucose DMEM condition, which mimicked T2D, in primary mouse hepatocytes. @@@ 2. Perifosine or rapamycin almost abolished the decrease of the Ces1d and Ces1e expression and the hydrolytic activity induced by the insulin in the primary mouse hepatocytes. @@@ 3. The responsiveness of human hepatoma (HepG2) cells to high insulin in high-glucose condition was similar to that of primary mouse hepatocytes in terms of the altered expression of carboxylesterases. @@@ 4. The knockdown of HIF-1 alpha or DEC1 with shRNA construct abrogated the decrease of the CES1 and CES2 expression induced by the insulin in high glucose condition in HepG2 cells. @@@ 5. Taken together, the decreased carboxylesterases expression and hydrolytic activity in T2D mice are through the Akt/mTOR/HIF-1 alpha/Stra13 (DEC1) pathway.

• 出版日期2015
• 单位南京医科大学