Decreased carboxylesterases expression and hydrolytic activity in type 2 diabetic mice through Akt/mTOR/HIF-1α/Stra13 pathway.
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.
['Chen|Ruini|R|', 'Wang|Yuwen|Y|', 'Ning|Rui|R|', 'Hu|Jinhua|J|', 'Liu|Wei|W|', 'Xiong|Jing|J|', 'Wu|Lili|L|', 'Liu|Jie|J|', 'Hu|Gang|G|', 'Yang|Jian|J|']
D000818:Animals D051792:Basic Helix-Loop-Helix Transcription Factors D001786:Blood Glucose D002265:Carboxylic Ester Hydrolases D003924:Diabetes Mellitus, Type 2 D004195:Disease Models, Animal D055785:Gene Knockdown Techniques D005947:Glucose D056945:Hep G2 Cells D022781:Hepatocytes D018398:Homeodomain Proteins D006801:Humans D006868:Hydrolysis D051795:Hypoxia-Inducible Factor 1, alpha Subunit D007328:Insulin D007422:Intestines D008099:Liver D008297:Male D008810:Mice, Inbred C57BL D050177:Overweight D010767:Phosphorylcholine D051057:Proto-Oncogene Proteins c-akt D012333:RNA, Messenger D034741:RNA, Small Interfering D015398:Signal Transduction D020123:Sirolimus D058570:TOR Serine-Threonine Kinases
type 2 diabetes Akt/mTOR/HIF-1α/Stra13 pathway carboxylesterase 1d (Ces1d) carboxylesterase 1e (Ces1e) insulin