PTEN influences insulin and lipid metabolism in bovine hepatocytes in vitro

The Journal of Dairy Research
Qinghua DengGuowen Liu

Abstract

Dairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor and also a negative regulator of insulin signaling and peripheral insulin sensitivity. We investigated the hypothesis that PTEN may affect the insulin pathway-mediated hepatic glucose and lipid metabolism in dairy cows. Adenovirus vectors that over-express and silence PTEN were constructed, and then transfected into hepatocytes isolated from calves to investigate the effect of PTEN on PI3K/AKT signaling pathway. PTEN silencing increased the phosphorylation of AKT and the expression of PI3K but decreased the phosphorylation of IRS1, which increased the phosphorylation levels of glycogen synthase kinase-3β (GSK-3β) and expression of sterol regulatory element-binding protein-1c (SREBP-1c). Increased GSK-3β phosphorylation further up-regulated expression of the key enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6-Pase) involved in gluconeogenesis. Furthermore, the expression of SREBP-1c target gene fatty acid synthase (FAS) also increased significantly. We further showed that P...Continue Reading

References

Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·Kohjiro UekiLewis C Cantley
Jun 17, 2004·The Journal of Clinical Investigation·Yasuo HorieToru Nakano
Apr 16, 2009·British Journal of Pharmacology·Geetha Vani RayasamAbhijit Ray
Jan 21, 2010·Physiological Reviews·Luc Tappy, Kim-Anne Lê
Jul 16, 2010·The Journal of Reproduction and Development·Stephen LeBlanc
Sep 28, 2010·World Journal of Gastroenterology : WJG·Marion PeyrouMichelangelo Foti
Feb 18, 2011·The Veterinary Journal·Zhi-Gang ZhangRi-He Zhang
Dec 12, 2012·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Shixin FuGuowen Liu
Mar 13, 2014·Nature Communications·Kohei UchimuraKenichiro Kitamura
May 24, 2014·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Qinghua DengXiaobing Li
Jun 7, 2014·Annual Review of Biochemistry·Carolyn A Worby, Jack E Dixon
Sep 23, 2014·Journal of Hepatology·Marion PeyrouMichelangelo Foti
Dec 4, 2014·Journal of Dairy Science·A J ItleM A G von Keyserlingk
Dec 3, 2015·Journal of Dairy Science·S MannD V Nydam
Jul 25, 2018·Frontiers in Endocrinology·Chien-Yu ChenBangyan L Stiles

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.