Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Biol Sci 2022; 18(5):1852-1864. doi:10.7150/ijbs.66314 This issue Cite

Research Paper

Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice

Zydrune Polianskyte-Prause1, Tuomas A. Tolvanen2, Sonja Lindfors1, Kanta Kon3, Laura C. Hautala1, Hong Wang2*, Tsutomu Wada3, Hiroshi Tsuneki3, Toshiyasu Sasaoka3, Sanna Lehtonen1,2✉

1. Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
2. Department of Pathology, University of Helsinki, Helsinki, Finland.
3. Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
*Current affiliation: Minerva Foundation Institute for Medical Research, Helsinki, Finland.

✉ Corresponding author: Prof. Sanna Lehtonen, University of Helsinki, Department of Pathology, Research Program for Clinical and Molecular Metabolism, P.O. Box 21, 00014 University of Helsinki, Finland, Phone: +358 50 4482798, Fax: +358 2941 26700, E- More

Citation:
Polianskyte-Prause Z, Tolvanen TA, Lindfors S, Kon K, Hautala LC, Wang H, Wada T, Tsuneki H, Sasaoka T, Lehtonen S. Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice. Int J Biol Sci 2022; 18(5):1852-1864. doi:10.7150/ijbs.66314. https://www.ijbs.com/v18p1852.htm
Other styles

File import instruction

Abstract

Graphic abstract

Ebselen, a multifunctional organoselenium compound, has been recognized as a potential treatment for diabetes-related disorders. However, the underlying mechanisms whereby ebselen regulates metabolic pathways remain elusive. We discovered that ebselen inhibits lipid phosphatase SHIP2 (Src homology 2 domain-containing inositol-5-phosphatase 2), an emerging drug target to ameliorate insulin resistance in diabetes. We found that ebselen directly binds to and inhibits the catalytic activity of the recombinant SHIP2 phosphatase domain and SHIP2 in cultured cells, the skeletal muscle and liver of the diabetic db/db mice, and the liver of the SHIP2 overexpressing (SHIP2-Tg) mice. Ebselen increased insulin-induced Akt phosphorylation in cultured myotubes, enhanced insulin sensitivity and protected liver tissue from lipid peroxidation and inflammation in the db/db mice, and improved glucose tolerance more efficiently than metformin in the SHIP2-Tg mice. SHIP2 overexpression abrogated the ability of ebselen to induce glucose uptake and reduce ROS production in myotubes and blunted the effect of ebselen to inhibit SHIP2 in the skeletal muscle of the SHIP2-Tg mice. Our data reveal ebselen as a potent SHIP2 inhibitor and demonstrate that the ability of ebselen to ameliorate insulin resistance and act as an antioxidant is at least in part mediated by the reduction of SHIP2 activity.

Keywords: insulin resistance, inflammation, lipid phosphatase, oxidative stress, type 2 diabetes

Citation styles

APA
Polianskyte-Prause, Z., Tolvanen, T.A., Lindfors, S., Kon, K., Hautala, L.C., Wang, H., Wada, T., Tsuneki, H., Sasaoka, T., Lehtonen, S. (2022). Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice. International Journal of Biological Sciences, 18(5), 1852-1864. https://doi.org/10.7150/ijbs.66314.

ACS
Polianskyte-Prause, Z.; Tolvanen, T.A.; Lindfors, S.; Kon, K.; Hautala, L.C.; Wang, H.; Wada, T.; Tsuneki, H.; Sasaoka, T.; Lehtonen, S. Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice. Int. J. Biol. Sci. 2022, 18 (5), 1852-1864. DOI: 10.7150/ijbs.66314.

NLM
Polianskyte-Prause Z, Tolvanen TA, Lindfors S, Kon K, Hautala LC, Wang H, Wada T, Tsuneki H, Sasaoka T, Lehtonen S. Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice. Int J Biol Sci 2022; 18(5):1852-1864. doi:10.7150/ijbs.66314. https://www.ijbs.com/v18p1852.htm

CSE
Polianskyte-Prause Z, Tolvanen TA, Lindfors S, Kon K, Hautala LC, Wang H, Wada T, Tsuneki H, Sasaoka T, Lehtonen S. 2022. Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice. Int J Biol Sci. 18(5):1852-1864.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use