PTEN: The Potential Therapeutic Target of Diabetes Mellitus

Authors

  • Ni Made Wiasty Sukanty Nutrition, Universitas Bumigora, Mataram
  • I Putu Bayu Agus Saputra Herbal Medicine dan Nutrigenomic, Universitas Islam Al-Azhar, Mataram
  • Lina Yunita Nutrition, Universitas Bumigora, Mataram

DOI:

https://doi.org/10.51967/tanesa.v24i1.2004

Keywords:

Diabetes mellitus, Insulin Resistance, Blood Glucose, PTEN, PI3K/Akt

Abstract

Diabetes mellitus is a metabolic disease characterized by high blood glucose levels. The cause of glucose control failure is decreased insulin production by pancreatic β-cells and insulin resistance. Both lead to the obstacle of glucose uptake into cells. The mechanism of glucose uptake into cells is crucial in carbohydrate metabolism. This mechanism aims to produce energy in the form of ATP. The main signaling pathway after the process of glucose uptake is the PI3K/Akt pathway. This pathway involves many proteins activated by phosphorylation mechanisms. One of the proteins involved in this pathway is PTEN, a PI3K regulator. PTEN activity can dephosphorylate PI3K so that the insulin signaling pathway becomes blocked and glucose cannot be uptaken into cells. It causes blood glucose levels to increase. The role of PTEN in inhibiting the PI3K/Akt pathway seems to be a crucial matter to observe. By inhibiting PTEN activity, the insulin signaling pathway is expected to work properly. We have searched, read, analyzed, and summarized various studies regarding the potential of PTEN to reduce diabetes mellitus cases. In some research articles, the use of active compounds and therapy using stem cells to inhibit PTEN activity has shown good progress in the insulin signaling pathway. Based on these, it can be an option to make PTEN a target for diabetes mellitus therapy.

References

Berbudi, A., Rahmadika, N., Tjahjadi, A. I., & Ruslami, R. (2019). Type 2 Diabetes and its Impact on the Immune System. Current Diabetes Reviews, 16(5), 442–449. https://doi.org/10.2174/1573399815666191024085838

Chen, C. Y., Chen, J., He, L., & Stiles, B. L. (2018). PTEN: Tumor Suppressor and Metabolic Regulator. Frontiers in Endocrinology, 9(JUL), 1–12. https://doi.org/10.3389/fendo.2018.00338

Chen, G., Fan, X. Y., Zheng, X. P., Jin, Y. L., Liu, Y., & Liu, S. C. (2020). Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice. Stem Cell Research and Therapy, 11(1), 1–13. https://doi.org/10.1186/s13287-020-01865-7

Cheng, M., Guo, Y., Zhong, W., Chen, X., & Guo, G. (2022). Abnormal Expression of microRNA-296-3p in Type 2 Diabetes Patients and its Role in Pancreatic β-Cells Function by Targeting Tensin Homolog Deleted on Chromosome Ten. In Biochemical Genetics (Vol. 60, Issue 1, pp. 39–53). https://doi.org/10.1007/s10528-021-10083-6

El-Zeftawy, M., Ghareeb, D., ElBealy, E. R., Saad, R., Mahmoud, S., Elguindy, N., El-kott, A. F., & El-Sayed, M. (2019). Berberine chloride ameliorated PI3K/Akt‐p/SIRT‐1/PTEN signaling pathway in insulin resistance syndrome induced in rats. Journal of Food Biochemistry, 43, e13049.

Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020). Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences, 21(17), 1–34. https://doi.org/10.3390/ijms21176275

Gao, J. R., Qin, X. J., Fang, Z. H., Li-Shan, Han, L. P., Hui-Jian, Guo, M. F., & Jiang, N. N. (2019). To explore the pathogenesis of vascular lesion of type 2 diabetes mellitus based on the PI3K/Akt signaling pathway. Journal of Diabetes Research, 2019. https://doi.org/10.1155/2019/4650906

Gong, L., Feng, D., Wang, T., Ren, Y., Liu, Y., & Wang, J. (2020). Inhibitors of α-amylase and α-glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia. Food Science and Nutrition, 8(12), 1–18. https://doi.org/10.1002/fsn3.1987

Gu, X., Wang, X. Q., Lin, M. J., Liang, H., Fan, S. Y., Wang, L., Yan, X., Liu, W., & Shen, F. X. (2019). Molecular interplay between microRNA-130a and PTEN in palmitic acid-mediated impaired function of endothelial progenitor cells: Effects of metformin. International Journal of Molecular Medicine, 43(5), 2187–2198. https://doi.org/10.3892/ijmm.2019.4140

Hossain, U., Das, A. K., Ghosh, S., & Sil, P. C. (2020). An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications. Food and Chemical Toxicology, 145. https://doi.org/10.1016/j.fct.2020.111738

Hu, W., Song, X., Yu, H., Sun, J., & Zhao, Y. (2020). Therapeutic Potentials of Extracellular Vesicles for the Treatment of Diabetes and Diabetic Complications. International Journal of Molecular Sciences, 21(14), 1–24. https://doi.org/10.3390/ijms21145163

Khokhar, M., Roy, D., Modi, A., Agarwal, R., Yadav, D., Purohit, P., & Sharma, P. (2020). Perspectives on the role of PTEN in diabetic nephropathy: an update. Critical Reviews in Clinical Laboratory Sciences, 57(7), 470–483. https://doi.org/10.1080/10408363.2020.1746735

Kjos, I., Vestre, K., Guadagno, N. A., Borg Distefano, M., & Progida, C. (2018). Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics. Biochimica et Biophysica Acta - Molecular Cell Research, 1865(10), 1397–1409. https://doi.org/10.1016/j.bbamcr.2018.07.009

Kushi, R., Hirota, Y., & Ogawa, W. (2021). Insulin resistance and exaggerated insulin sensitivity triggered by single-gene mutations in the insulin signaling pathway. Diabetology International, 12(1), 62–67. https://doi.org/10.1007/s13340-020-00455-5

Li, J., Qi, X., Wang, X., Li, W., Li, Y., & Zhou, Q. (2020). PTEN inhibition facilitates diabetic corneal epithelial regeneration by reactivating akt signaling pathway. Translational Vision Science and Technology, 9(3), 1–11. https://doi.org/10.1167/tvst.9.3.5

Li, Y. Z., Di Cristofano, A., & Woo, M. (2020). Metabolic Role of PTEN in Insulin Signaling and Resistance. Cold Spring Harbor Perspectives in Medicine, 10(8), 1–17. https://doi.org/10.1101/cshperspect.a036137

Maity, S., Das, F., Ghosh-Choudhury, N., Kasinath, B. S., & Ghosh Choudhury, G. (2019). High glucose increases miR-214 to power a feedback loop involving PTEN and the Akt/mTORC1 signaling axis. FEBS Letters, 593(16), 2261–2272. https://doi.org/10.1002/1873-3468.13505

McLoughlin, N. M., Mueller, C., & Grossmann, T. N. (2018). The Therapeutic Potential of PTEN Modulation: Targeting Strategies from Gene to Protein. Cell Chemical Biology, 25(1), 19–29. https://doi.org/10.1016/j.chembiol.2017.10.009

Oguntibeju, O. O. (2019). Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. International Journal of Physiology, Pathophysiology and Pharmacology, 11(3), 45–63. http://www.ncbi.nlm.nih.gov/pubmed/31333808%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6628012

Roden, M., & Shulman, G. I. (2019). The integrative biology of type 2 diabetes. Nature, 576(7785), 51–60. https://doi.org/10.1038/s41586-019-1797-8

Saltiel, A. R. (2021). Insulin signaling in health and disease. Journal of Clinical Investigation, 131(1), e142241. https://doi.org/10.1172/JCI142241

Wang, H., Feng, Z., Ie, J., Wen, F., Jv, M., Liang, T., Li, J., Wang, Y., Zuo, Y., Li, S., Li, R., Li, Z., Zhang, B., Liang, X., Liu, S., Shi, W., & Wang, W. (2018). Podocyte-specific knockin of PTEN protects kidney from hyperglycemia. American Journal of Physiology - Renal Physiology, 314(6), F1096–F1107. https://doi.org/10.1152/ajprenal.00575.2017

Xu, B., Li, Z., Zeng, T., Zhan, J., Wang, S., Ho, C. T., & Li, S. (2022). Bioactives of Momordica charantia as Potential Anti-Diabetic/Hypoglycemic Agents. Molecules, 27(7), 1–17. https://doi.org/10.3390/molecules27072175

Xue J, Gao J, Gu Y, Wang A, Yu S, Li B, Yin Y, Wang J, Su W, Zhang H, Ren W, Gu W, Lv Z, Mu Y, C. Y. (2022). Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes. Stem Cell Res Ther, 13(1), 109. https://doi.org/10.1186/s13287-022-02791-6

Yin, L., Cai, W. J., Chang, X. Y., Li, J., Zhu, L. Y., Su, X. H., Yu, X. F., & Sun, K. (2018). Analysis of PTEN expression and promoter methylation in Uyghur patients with mild type 2 diabetes mellitus. Medicine (United States), 97(49), 1–9. https://doi.org/10.1097/MD.0000000000013513

Zhang, Z. Y., Miao, L. F., Qian, L. L., Wang, N., Qi, M. M., Zhang, Y. M., Dang, S. P., Wu, Y., & Wang, R. X. (2019). Molecular Mechanisms of Glucose Fluctuations on Diabetic Complications. Frontiers in Endocrinology, 10(September), 1–11. https://doi.org/10.3389/fendo.2019.00640

Downloads

Published

2023-06-25

How to Cite

Sukanty, N. M. W., Saputra, I. P. B. A., & Yunita, L. (2023). PTEN: The Potential Therapeutic Target of Diabetes Mellitus. Buletin Poltanesa, 24(1), 109–114. https://doi.org/10.51967/tanesa.v24i1.2004

Issue

Section

Health Science