Protein-Protein Interaction Analysis to Identify New Drug Targets for Diabetes
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Diabetes, Drug Targets, Protein Interactions
Abstract
The background of this study focuses on diabetes, a chronic metabolic disease characterized by impaired glucose and insulin regulation. Although existing therapies are available, insulin resistance and other complications remain a major challenge. The purpose of this study is to identify new drug targets through the analysis of protein interactions that play a role in the pathogenesis of diabetes. The method used is protein interaction network analysis (PPI) using public databases such as STRING and BioGRID to map the interaction between proteins related to glucose metabolism and insulin. The results of this study identified more than 150 proteins that interact with each other in the regulatory pathways of glucose and insulin metabolism, with several new proteins found to have the potential to be drug targets to overcome insulin resistance. The study concludes that a protein interaction-based approach can open up opportunities to develop new therapies that are more specific and effective in managing diabetes. Further development should be undertaken for the validation of these findings in animal models and clinical trials to confirm their effectiveness as a diabetes therapy.
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References
American Diabetes Association. (2020a). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43(Supplement_1), S14–S31. https://doi.org/10.2337/dc20-S002
American Diabetes Association. (2020b). 5. Facilitating Behavior Change and Well-being to Improve Health Outcomes: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43(Supplement_1), S48–S65. https://doi.org/10.2337/dc20-S005
American Diabetes Association. (2020c). 6. Glycemic Targets: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43(Supplement_1), S66–S76. https://doi.org/10.2337/dc20-S006
American Diabetes Association. (2020d). 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43(Supplement_1), S111–S134. https://doi.org/10.2337/dc20-S010
American Diabetes Association. (2020e). 13. Children and Adolescents: Standards of Medical Care in Diabetes?2020. Diabetes Care, 43(Supplement_1), S163–S182. https://doi.org/10.2337/dc20-S013
American Diabetes Association. (2020f). 14. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43(Supplement_1), S183–S192. https://doi.org/10.2337/dc20-S014
American Diabetes Association. (2020g). 15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43(Supplement_1), S193–S202. https://doi.org/10.2337/dc20-S015
American Diabetes Association. (2021a). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care, 44(Supplement_1), S15–S33. https://doi.org/10.2337/dc21-S002
American Diabetes Association. (2021b). 6. Glycemic Targets: Standards of Medical Care in Diabetes—2021. Diabetes Care, 44(Supplement_1), S73–S84. https://doi.org/10.2337/dc21-S006
American Diabetes Association. (2021c). 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes—2021. Diabetes Care, 44(Supplement_1), S151–S167. https://doi.org/10.2337/dc21-S011
American Diabetes Association. (2022). Standards of Medical Care in Diabetes—2022 Abridged for Primary Care Providers. Clinical Diabetes, 40(1), 10–38. https://doi.org/10.2337/cd22-as01
American Diabetes Association Professional Practice Committee. (2022a). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2022. Diabetes Care, 45(Supplement_1), S17–S38. https://doi.org/10.2337/dc22-S002
American Diabetes Association Professional Practice Committee. (2022b). 6. Glycemic Targets: Standards of Medical Care in Diabetes—2022. Diabetes Care, 45(Supplement_1), S83–S96. https://doi.org/10.2337/dc22-S006
American Diabetes Association Professional Practice Committee. (2022c). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2022. Diabetes Care, 45(Supplement_1), S125–S143. https://doi.org/10.2337/dc22-S009
American Diabetes Association Professional Practice Committee. (2022d). 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2022. Diabetes Care, 45(Supplement_1), S144–S174. https://doi.org/10.2337/dc22-S010
American Diabetes Association Professional Practice Committee. (2022e). 11. Chronic Kidney Disease and Risk Management: Standards of Medical Care in Diabetes—2022. Diabetes Care, 45(Supplement_1), S175–S184. https://doi.org/10.2337/dc22-S011
American Diabetes Association Professional Practice Committee, ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Gaglia, J. L., Hilliard, M. E., Johnson, E. L., Khunti, K., Lingvay, I., Matfin, G., McCoy, R. G., Perry, M. L., Pilla, S. J., Polsky, S., Prahalad, P., Pratley, R. E., … Gabbay, R. A. (2024). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024. Diabetes Care, 47(Supplement_1), S20–S42. https://doi.org/10.2337/dc24-S002
Anker, S. D., Butler, J., Filippatos, G., Khan, M. S., Marx, N., Lam, C. S. P., Schnaidt, S., Ofstad, A. P., Brueckmann, M., Jamal, W., Bocchi, E. A., Ponikowski, P., Perrone, S. V., Januzzi, J. L., Verma, S., Böhm, M., Ferreira, J. P., Pocock, S. J., Zannad, F., … On behalf of the EMPEROR-Reduced Trial Committees and Investigators. (2021). Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status: Results From the EMPEROR-Reduced Trial. Circulation, 143(4), 337–349. https://doi.org/10.1161/CIRCULATIONAHA.120.051824
Barnes, J. A., Eid, M. A., Creager, M. A., & Goodney, P. P. (2020). Epidemiology and Risk of Amputation in Patients With Diabetes Mellitus and Peripheral Artery Disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 40(8), 1808–1817. https://doi.org/10.1161/ATVBAHA.120.314595
Berbudi, A., Rahmadika, N., Tjahjadi, A. I., & Ruslami, R. (2020). Type 2 Diabetes and its Impact on the Immune System. Current Diabetes Reviews, 16(5), 442–449. https://doi.org/10.2174/1573399815666191024085838
Buse, J. B., Wexler, D. J., Tsapas, A., Rossing, P., Mingrone, G., Mathieu, C., D’Alessio, D. A., & Davies, M. J. (2020). 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 43(2), 487–493. https://doi.org/10.2337/dci19-0066
Capehorn, M. S., Catarig, A.-M., Furberg, J. K., Janez, A., Price, H. C., Tadayon, S., Vergès, B., & Marre, M. (2020). Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes & Metabolism, 46(2), 100–109. https://doi.org/10.1016/j.diabet.2019.101117
Chen, Y., Yang, D., Cheng, B., Chen, J., Peng, A., Yang, C., Liu, C., Xiong, M., Deng, A., Zhang, Y., Zheng, L., & Huang, K. (2020). Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication. Diabetes Care, 43(7), 1399–1407. https://doi.org/10.2337/dc20-0660
Davies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., Rossing, P., Tankova, T., Tsapas, A., & Buse, J. B. (2022). Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 45(11), 2753–2786. https://doi.org/10.2337/dci22-0034
De Boer, I. H., Khunti, K., Sadusky, T., Tuttle, K. R., Neumiller, J. J., Rhee, C. M., Rosas, S. E., Rossing, P., & Bakris, G. (2022). Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care, 45(12), 3075–3090. https://doi.org/10.2337/dci22-0027
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Das, S. R., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Kosiborod, M., Leon, J., Lyons, S. K., Perry, M. L., Prahalad, P., Pratley, R. E., … Gabbay, R. A. (2023). 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023. Diabetes Care, 46(Supplement_1), S158–S190. https://doi.org/10.2337/dc23-S010
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Gaglia, J. L., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Leon, J., Lyons, S. K., Perry, M. L., Prahalad, P., Pratley, R. E., Seley, J. J., … American Diabetes Association. (2023). 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—2023. Diabetes Care, 46(Supplement_1), S19–S40. https://doi.org/10.2337/dc23-S002
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Leon, J., Lyons, S. K., Perry, M. L., Prahalad, P., Pratley, R. E., Seley, J. J., Stanton, R. C., & Gabbay, R. A. (2023a). 6. Glycemic Targets: Standards of Care in Diabetes—2023. Diabetes Care, 46(Supplement_1), S97–S110. https://doi.org/10.2337/dc23-S006
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Leon, J., Lyons, S. K., Perry, M. L., Prahalad, P., Pratley, R. E., Seley, J. J., Stanton, R. C., & Gabbay, R. A. (2023b). 7. Diabetes Technology: Standards of Care in Diabetes — 2023. Diabetes Care, 46(Supplement_1), S111–S127. https://doi.org/10.2337/dc23-S007
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Leon, J., Lyons, S. K., Perry, M. L., Prahalad, P., Pratley, R. E., Seley, J. J., Stanton, R. C., & Gabbay, R. A. (2023c). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2023. Diabetes Care, 46(Supplement_1), S140–S157. https://doi.org/10.2337/dc23-S009
Goldenberg, J. Z., Day, A., Brinkworth, G. D., Sato, J., Yamada, S., Jönsson, T., Beardsley, J., Johnson, J. A., Thabane, L., & Johnston, B. C. (2021). Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: Systematic review and meta-analysis of published and unpublished randomized trial data. BMJ, m4743. https://doi.org/10.1136/bmj.m4743
Holt, R. I. G., DeVries, J. H., Hess-Fischl, A., Hirsch, I. B., Kirkman, M. S., Klupa, T., Ludwig, B., Nørgaard, K., Pettus, J., Renard, E., Skyler, J. S., Snoek, F. J., Weinstock, R. S., & Peters, A. L. (2021). The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 44(11), 2589–2625. https://doi.org/10.2337/dci21-0043
Huang, I., Lim, M. A., & Pranata, R. (2020). Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(4), 395–403. https://doi.org/10.1016/j.dsx.2020.04.018
Kumar, A., Arora, A., Sharma, P., Anikhindi, S. A., Bansal, N., Singla, V., Khare, S., & Srivastava, A. (2020). Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(4), 535–545. https://doi.org/10.1016/j.dsx.2020.04.044
Lee, M. M. Y., Brooksbank, K. J. M., Wetherall, K., Mangion, K., Roditi, G., Campbell, R. T., Berry, C., Chong, V., Coyle, L., Docherty, K. F., Dreisbach, J. G., Labinjoh, C., Lang, N. N., Lennie, V., McConnachie, A., Murphy, C. L., Petrie, C. J., Petrie, J. R., Speirits, I. A., … Sattar, N. (2021). Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF). Circulation, 143(6), 516–525. https://doi.org/10.1161/CIRCULATIONAHA.120.052186
Shi, Q., Zhang, X., Jiang, F., Zhang, X., Hu, N., Bimu, C., Feng, J., Yan, S., Guan, Y., Xu, D., He, G., Chen, C., Xiong, X., Liu, L., Li, H., Tao, J., Peng, Z., & Wang, W. (2020). Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. Diabetes Care, 43(7), 1382–1391. https://doi.org/10.2337/dc20-0598
Singh, A. K., Gupta, R., Ghosh, A., & Misra, A. (2020). Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(4), 303–310. https://doi.org/10.1016/j.dsx.2020.04.004
Singh, A. K., Singh, A., Shaikh, A., Singh, R., & Misra, A. (2020). Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(3), 241–246. https://doi.org/10.1016/j.dsx.2020.03.011
Zelniker, T. A., Bonaca, M. P., Furtado, R. H. M., Mosenzon, O., Kuder, J. F., Murphy, S. A., Bhatt, D. L., Leiter, L. A., McGuire, D. K., Wilding, J. P. H., Budaj, A., Kiss, R. G., Padilla, F., Gause-Nilsson, I., Langkilde, A. M., Raz, I., Sabatine, M. S., & Wiviott, S. D. (2020). Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial. Circulation, 141(15), 1227–1234. https://doi.org/10.1161/CIRCULATIONAHA.119.044183
Zhang, Y., Lazzarini, P. A., McPhail, S. M., Van Netten, J. J., Armstrong, D. G., & Pacella, R. E. (2020). Global Disability Burdens of Diabetes-Related Lower-Extremity Complications in 1990 and 2016. Diabetes Care, 43(5), 964–974. https://doi.org/10.2337/dc19-1614
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