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

Abstract

• 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-1α/ 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-1α 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-1α/Stra13 (DEC1) pathway.

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

Acknowledgements

The authors thank Dr. Bingfang Yan of University of Rhode Island for donating the DEC1 antibody.

Declaration of interest

The authors report that they have no conflicts of interest. This study was supported by the Natural Science Foundation of China (Nos. 81173128, 81102457, 81373443, and 81302855), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (2012323411000), the Major Project of Jiangsu Provincial Department of Education (No. 13KJA310003), the Ministry and Education of PRC (20123234110005).