Insulin regulates glucose consumption and lactate production through reactive oxygen species and pyruvate kinase M2.

Authors

Qi Li, Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow
Xue Liu, Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow
Yu Yin, Department of Pathology, Cancer Center, Nanjing Medical University; Department of Pathology, Anhui Medical University, Hefei 230032, ChinaFollow
Ji-Tai Zheng, Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow
Cheng-Fei Jiang, Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow
Jing Wang, Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow
Hua Shen, Department of Oncology, First Affiliated Hospital of Nanjing Medical UniversityFollow
Chong-Yong Li, Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow
Min Wang, Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow
Ling-Zhi Liu, Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Bing-Hua Jiang, Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Pathology, Cancer Center, Nanjing Medical UniversityFollow

Document Type

Article

Publication Date

2014

Comments

This article has been peer reviewed. It is the author’s final published version in Oxidative Medicine and Cellular Longevity Volume 5, 2014, Article number 504953.

The published version is available at DOI: 10.1155/2014/504953. Copyright © Qi Li et al.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Although insulin is known to regulate glucose metabolism and closely associate with liver cancer, the molecular mechanisms still remain to be elucidated. In this study, we attempt to understand the mechanism of insulin in promotion of liver cancer metabolism. We found that insulin increased pyruvate kinase M2 (PKM2) expression through reactive oxygen species (ROS) for regulating glucose consumption and lactate production, key process of glycolysis in hepatocellular carcinoma HepG2 and Bel7402 cells. Interestingly, insulin-induced ROS was found responsible for the suppression of miR-145 and miR-128, and forced expression of either miR-145 or miR-128 was sufficient to abolish insulin-induced PKM2 expression. Furthermore, the knockdown of PKM2 expression also inhibited cancer cell growth and insulin-induced glucose consumption and lactate production, suggesting that PKM2 is a functional downstream effecter of insulin. Taken together, this study would provide a new insight into the mechanism of insulin-induced glycolysis.

Recommended Citation

Li, Qi; Liu, Xue; Yin, Yu; Zheng, Ji-Tai; Jiang, Cheng-Fei; Wang, Jing; Shen, Hua; Li, Chong-Yong; Wang, Min; Liu, Ling-Zhi; and Jiang, Bing-Hua, "Insulin regulates glucose consumption and lactate production through reactive oxygen species and pyruvate kinase M2." (2014). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 147.
https://jdc.jefferson.edu/pacbfp/147

PubMed ID

24895527