Mechanisms of Ferroptosis in Pancreatic β-Cell Dysfunction in Diabetes and Exploration of Therapeutic Targets

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[4]       Novoselova, E. G., Lunin, S. M., Khrenov, M. O., Glushkova, O. V., Novoselova, T. V., and Parfenyuk, S. B. 2023. “The Possible Role of β-Cell Senescence in the Development of Type 2 Diabetes Mellitus. Cellular Physiology and Biochemistry.” International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology 57 (1): 34-48.

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[7]       Stancic, A., Saksida, T., Markelic, M., Vucetic, M., Grigorov, I., Martinovic, V., Gajic, D., Ivanovic, A., Velickovic, K., Savic, N., and Otasevic, V. 2022. “Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions.” Oxidative Medicine and Cellular Longevity: 3873420.

[8]       Díaz-López, A., Iglesias-Vázquez, L., Pallejà-Millán, M., Rey Reñones, C., Flores Mateo, G., and Arija, V. 2020. “Association Between Iron Status and Incident Type 2 Diabetes: A Population-Based Cohort Study.” Nutrients 12 (11): 3249.

[9]       Ding, Y., and Wu, Q. 2023. “1,25D/VDR Inhibits Pancreatic β-cell Ferroptosis by Downregulating FOXO1 Expression in Diabetes Mellitus.” Cellular Signaling 105: 110564.

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[11]    Saad, H. M., Salem, E. A., Elhussieny, O., Waheeb, T. S., and Elsayed, A. E. 2025. “Crosstalk Between Ferroptosis and miRNA in Type 2 Diabetes Mellitus and Possible Therapeutic Targeting.” European Journal of Medical Research 30 (1): 982.

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[13]    Li, D., Jiang, C., Mei, G., Zhao, Y., Chen, L., Liu, J., Tang, Y., Gao, C., and Yao, P. 2020. “Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes.” Nutrients 12 (10): 2954.

[14]    Sha, W., Hu, F., Xi, Y., Chu, Y., and Bu, S. 2021. “Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus.” Journal Of Diabetes Research 2021: 9999612.

[15]    Krümmel, B., von Hanstein, A. S., Plötz, T., Lenzen, S., and Mehmeti, I. 2022. “Differential Effects of Saturated and Unsaturated Free Fatty Acids on Ferroptosis in Rat β-cells.” The Journal of Nutritional Biochemistry 106: 109013.

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[18]    Zhao, H., Li, R., Guo, X., Kang, J., Li, H., Wang, X., Wang, Y., Cui, H., Lv, S., Wen, W., and Zhang, Z. 2025. “Mechanism of Plantamajoside in Inhibiting Ferroptosis of Pancreatic β cells and Treatment of T2DM via Activation of the xCT/GPX4 Pathway.” PloS One 20 (6): e0325674.

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[20]    Yoo, S., Kim, D., Kim, M., Bae, J. Y., Lee, S. A., Kim, E. T., and Koh, G. 2025. “OTUB1 Modulates Ferroptosis by Regulating SLC7A11 Ubiquitination in Pancreatic β-Cells.” FASEB Journal 39 (20): e71128.

[21]    Díaz-López, A., Iglesias-Vázquez, L., Pallejà-Millán, M., Rey Reñones, C., Flores Mateo, G., and Arija, V. 2020. “Association between Iron Status and Incident Type 2 Diabetes: A Population-Based Cohort Study.” Nutrients 12 (11): 3249.

[22]    Sun, Y., Bai, Y. P., Wang, D. G., Xing, Y. J., Zhang, T., Wang, W., Zhou, S. M., Cheng, J. H., Chang, W. W., Kong, X., Yao, X. M., and Guo, L. Q. 2023. Protective Effects of Metformin on Pancreatic β-cell Ferroptosis in Type 2 Diabetes in Vivo.” Biomedecine & Pharmacotherapie 168: 115835.

[23]    Wang, N., Wang, J., Wu, Y., Qu, M., Hong, J., Cui, Z., Chen, Y., & Zhang, R. (2025). “Cynarin Counteracts Lipotoxicity in Pancreatic β-Cells Via Inhibiting Palmitate-Induced Apoptosis and Linoleic Acid-Provoked Ferroptosis.” Plant Foods for Human Nutrition (Dordrecht, Netherlands) 80 (3): 139.

[24]    Miao, R., Fang, X., Zhang, Y., Wei, J., Zhang, Y., and Tian, J. 2023. “Iron Metabolism and Ferroptosis in Type 2 Diabetes Mellitus and Complications: Mechanisms and Therapeutic Opportunities.” Cell Death & Disease 14 (3): 186.

[25]    Yoo, S., Kim, D., Kim, M., Bae, J. Y., Lee, S. A., Kim, E. T., and Koh, G. 2025. “OTUB1 Modulates Ferroptosis by Regulating SLC7A11 Ubiquitination in Pancreatic β-Cells.” FASEB Journal 39 (20): e71128.

[26]    Ding, Y., and Wu, Q. 2023. “1,25D/VDR Inhibits Pancreatic β Cell Ferroptosis by Downregulating FOXO1 Expression in Diabetes Mellitus.” Cellular Signaling 105: 110564.

[27]    Li, H., Zhang, H., Wang, T., Zhang, L., Wang, H., Lu, H., Yang, R., and Ding, Y. 2024. “Grape Seed Proanthocyanidins Protect Pancreatic β Cells Against Ferroptosis via the Nrf2 Pathway in Type 2 Diabetes.” Biological Trace Element Research 202 (12): 5531-5544.

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[31]    Krümmel, B., von Hanstein, A. S., Plötz, T., Lenzen, S., and Mehmeti, I. 2022. “Differential Effects of Saturated and Unsaturated Free Fatty Acids on Ferroptosis in Rat β-cells.” The Journal of Nutritional Biochemistry 106: 109013.

[32]    Li, H., Zhang, H., Wang, T., Zhang, L., Wang, H., Lu, H., Yang, R., and Ding, Y. 2024. “Grape Seed Proanthocyanidins Protect Pancreatic β Cells Against Ferroptosis via the Nrf2 Pathway in Type 2 Diabetes.” Biological Trace Element Research 202 (12): 5531-5544.

[33]    Prasad, M. K., Jayasuriya, R., and Ramkumar K. M. 2026. Polydatin Attenuates Ferroptosis in Pancreatic β- Cells via Activation of the GPx4-Nrf2 Axis under Hyperglycemic Conditions. The Journal of nutrition, 156(2), 101284.

[34]    Stancic, A., Saksida, T., Markelic, M., Vucetic, M., Grigorov, I., Martinovic, V., Gajic, D., Ivanovic, A., Velickovic, K., Savic, N., and Otasevic, V. 2022. “Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions.” Oxidative Medicine and Cellular Longevity 2022: 3873420.

[35]    Novoselova, E. G., Lunin, S. M., Khrenov, M. O., Glushkova, O. V., Novoselova, T. V., & Parfenyuk, S. B. 2023. “The Possible Role of Β-Cell Senescence in the Development of Type 2 Diabetes Mellitus.” Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology 57 (1): 34-48.

[36]    Sun, Y., Bai, Y. P., Wang, D. G., Xing, Y. J., Zhang, T., Wang, W., Zhou, S. M., Cheng, J. H., Chang, W. W., Kong, X., Yao, X. M., and Guo, L. Q. 2023. “Protective Effects of Metformin on Pancreatic β-cell Ferroptosis in Type 2 Diabetes in Vivo.” Biomedecine & Pharmacotherapie 168: 115835.

[37]    Prasad, M. K., Jayasuriya, R., and Ramkumar, K. M. 2026. “Polydatin Attenuates Ferroptosis in Pancreatic β-Cells via Activation of the GPx4-Nrf2 Axis under Hyperglycemic Conditions.” The Journal of Nutrition 156 (2): 101284.

[38]    Novoselova, E. G., Lunin, S. M., Khrenov, M. O., Glushkova, O. V., Novoselova, T. V., and Parfenyuk, S. B. 2023. “The Possible Role of Β-Cell Senescence in the Development of Type 2 Diabetes Mellitus.” Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology 57 (1): 34-48.

[39]    Zhang, Y., Han, S., Liu, C., Zheng, Y., Li, H., Gao, F., Bian, Y., Liu, X., Liu, H., Hu, S., Li, Y., Chen, Z. J., Zhao, S., and Zhao, H. 2023. “THADA Inhibition in Mice Protects Against Type 2 Diabetes Mellitus by Improving Pancreatic β-cell Function and Preserving β-cell Mass.” Nature Communications 14 (1): 1020.

[40]    Liu, J., Zhang, Y., Shi, D., He, C., and Xia, G. 2023. “Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic β-Cell Impairment.” Experimental and Clinical Endocrinology & Diabetes 131 (12): 656-666.

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[43]    Liu, J., Zhang, Y., Shi, D., He, C., and Xia, G. 2023. “Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic β-Cell Impairment.” Experimental And Clinical Endocrinology & Diabetes 131 (12): 656-666.

[44]    Saad, H. M., Salem, E. A., Elhussieny, O., Waheeb, T. S., and Elsayed, A. E. 2025. “Crosstalk Between Ferroptosis and miRNA in Type 2 Diabetes Mellitus and Possible Therapeutic Targeting.” European Journal of Medical Research 30 (1): 982.

[45]    Li, D., Jiang, C., Mei, G., Zhao, Y., Chen, L., Liu, J., Tang, Y., Gao, C., and Yao, P. 2020. “Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes.” Nutrients 12 (10): 2954.

[46]    Wang, N., Wang, J., Wu, Y., Qu, M., Hong, J., Cui, Z., Chen, Y., and Zhang R. 2025. “Cynarin Counteracts Lipotoxicity in Pancreatic β-Cells Via Inhibiting Palmitate-Induced Apoptosis and Linoleic Acid-Provoked Ferroptosis.” Plant Foods for Human Nutrition (Dordrecht, Netherlands) 80 (3): 139.

[47]    Sha, W., Hu, F., Xi, Y., Chu, Y., and Bu, S. 2021. “Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus.” Journal of Diabetes Research 2021: 9999612.

[48]    Zhang, Y., Han, S., Liu, C., Zheng, Y., Li, H., Gao, F., Bian, Y., Liu, X., Liu, H., Hu, S., Li, Y., Chen, Z. J., Zhao, S., and Zhao, H. 2023. “THADA Inhibition in Mice Protects Against Type 2 Diabetes Mellitus by Improving Pancreatic β-cell Function and Preserving β-cell Mass.” Nature Communications 14 (1): 1020.

[49]    Chen J., Fei S., and Chan L. W. C. et al. 2025. “Inflammatory Signaling Pathways in Pancreatic β-cell: New Insights into Type 2 Diabetes Pathogenesis.” Pharmacological Research 216: 107776.

[50]    Yang, H., Chen, Y., Wu, G., Ren, P., Chen, T., Liu, J., Zhang, B., Ma, X., Jiang, F., Li, Y., Tao, L., and Shen, X. 2025. “Investigating the Role of 1,8-Cineole in Mitigating Ferroptosis in a HFSD/STZ Diabetes Mellitus Type 2-Induced Model: A GEO Data Analysis Approach.” European Journal of Pharmacology 1002: 177846.

[51]    Zhang, S., Liu, X., Wang, J., Yuan, F., and Liu, Y. 2022. “Targeting Ferroptosis with miR-144-3p to Attenuate Pancreatic β Cells Dysfunction via Regulating USP22/SIRT1 in Type 2 Diabetes. Diabetology & Metabolic Syndrome 14 (1): 89.

[52]    Wu, F., Shang, C., Jin, T., and Shi, L. 2023. “Hispidin Inhibits Ferroptosis Induced by High Glucose via the miR-15b-5p/GLS2 Axis in Pancreatic Beta Cells.” Evidence-based Complementary and Alternative Medicine 2023: 9428241.

[53]    Zhang, Q. W., Wang, Y., Tong, Z. Y., Li, C. P., and He, L. P. 2024. “Vitamin D May Play a Vital Role in Alleviating Type 2 Diabetes Mellitus by Modulating the Ferroptosis Signaling Pathway.” Hormone and Metabolic Research 56 (3): 193-196.