Molecular Docking of Gamma Amino Butyric Acid GABA on Rattus Norvegicus B-receptor as Antidiabetic

Authors

Meti Indrowati , Harlita , Umi Fatmawati , Joko Ariyanto , Estu Retnaningtyas

DOI:

10.29303/jppipa.v10i7.8044

Published:

2024-07-25

Issue:

Vol. 10 No. 7 (2024): July: In Press

Keywords:

Antidiabetic, GABA, GABA B receptor, Molecular docking, Rattus norvegicus

Research Articles

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Indrowati, M., Harlita, Fatmawati, U., Ariyanto, J., & Retnaningtyas, E. (2024). Molecular Docking of Gamma Amino Butyric Acid GABA on Rattus Norvegicus B-receptor as Antidiabetic. Jurnal Penelitian Pendidikan IPA, 10(7), 3858–3865. https://doi.org/10.29303/jppipa.v10i7.8044
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Abstract

Earlier research reported that GABA had a correlation with diabetes in processes of glucose homeostasis. This study aims to identify the validity of B-receptor Rattus norvegicus as GABA protein target, modeling the structure and knowing the binding affinity between GABA and B-receptor Rattus norvegicus through molecular docking.   The research was carried out using in-silico method.  The interaction of GABA with the target protein was determined using SuperPred, followed by modeling the protein target using SwissadMe. Ramachandran Plot and Errat Procheck are used to determine the validity of the protein target. Molecular docking was determined using Pyrx and PyMol. The results showed that GABA binding to the B- receptor Rattus norvegicus has biological activity as glucose oxidase inhibitor and antidiabetic.  The conclusion are: B-receptor Rattus norvegicus is a valid protein target for binding to GABA; there are four 3-dimensional models of B-receptor Rattus norvegicus and the best model has 98.43% sequence identity; the binding affinity of GABA (ligand) on B-receptor Rattus norvegicus from the best model is -3.4 kcal/mol energy, 1.773 RMSD lower bound, and 1.81 RMSD upper bound. It is suggested that this research might be used as an empirical basis to further investigate GABA as antidiabetic.

References

Al-Kuraishy, H. M., Hussian, N. R., Al-Naimi, M. S., Al-Gareeb, A. I., Al-Mamorri, F., & Al-Buhadily, A. K. (2021). The Potential Role of Pancreatic γ-Aminobutyric Acid (GABA) in Diabetes Mellitus: A Critical Reappraisal. International Journal of Preventive Medicine, 12(19), 1–7. https://doi.org/10.4103/ijpvm.IJPVM_278_19

Bare, Y., & Fatchiyah, F. (2018). Profil Protein pada Organ Tikus (Rattus norvegicus) Model Diabetes Melitus Tipe 2 (DMT2. Biota: Biologi Dan Pendidikan Biologi, 11(1), 1–12. https://doi.org/10.20414/jb.v11i1.95

Brohan, J., & Goudra, B. G. (2017). The Role of GABA Receptor Agonists in Anesthesia and Sedation. CNS Drugs, 31(10), 845–856. https://doi.org/10.1007/s40263-017-0463-7

Choat, H. M., Martin, A., Mick, G. J., Heath, K. E., Tse, H. M., McGwin, G., & McCormick, K. L. (2019). Effect of gamma aminobutyric acid (GABA) or GABA with glutamic acid decarboxylase (GAD) on the progression of type 1 diabetes mellitus in children: Trial design and methodology. Contemporary Clinical Trials, 82, 93–100. https://doi.org/10.1016/J.CCT.2019.06.007

Daems, C., Welsch, S., Boughaleb, H., Vanderroost, J., Robert, A., Sokal, E., & Lysy, P. A. (2019). Early Treatment with Empagliflozin and GABA Improves β -Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice. Journal of Diabetes Research. https://doi.org/10.1155/2019/2813489

Eltahawy, N. A., Saada, H. N., & Hammad, A. S. (2017). Gamma Amino Butyric Acid Attenuates Brain Oxidative Damage Associated with Insulin Alteration in Streptozotocin-Treated Rats. Indian Journal of Clinical Biochemistry: IJCB, 32(2), 207–213. https://doi.org/10.1007/s12291-016-0597-2

Fanisah, K., Setiawan, I., Parlindungan, D., Karyadi, B., Defianti, A., & Yani, A. P. (2023). Identification of the Diversity of Medicinal Plants Used by Battra in North Bengkulu. Jurnal Penelitian Pendidikan IPA, 9(10), 7969–7978. https://doi.org/10.29303/jppipa.v9i10.3876

Gaba, R., Mehta, P., & Balasubramanyam, A. (2019). Evaluation and management of ketosis-prone diabetes. Expert Review of Endocrinology and Metabolism, 14(1), 43–48. https://doi.org/10.1080/17446651.2019.1561270

Ghit, A., Assal, D., Al-Shami, A. S., & Hussein, D. E. E. (2021). GABAA receptors: structure, function, pharmacology, and related disorders. Journal of Genetic Engineering and Biotechnology, 19(1), 123. https://doi.org/10.1186/s43141-021-00224-0

Hosseini, D. A., Sharifi, M., & Soltani, N. (2021). GABA administration improves liver function and insulin resistance in offspring of type 2 diabetic rats. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-02324-w

Indrowati, M., Pratiwi, R., Rumiyati, & Astuti, P. (2017). Levels of Blood Glucose and Insulin Expression of Beta-cells in Streptozotocin-induced Diabetic Rats Treated with Ethanolic Extract of Artocarpus altilis Leaves and GABA. Pakistan Journal of Biological Sciences: PJBS, 20(1), 28–35. https://doi.org/10.3923/pjbs.2017.28.35

International Diabetes Federation, I. (2021). Diabetes around the world in 2021.IDF Diabetes Atlas. Retrieved from https://diabetesatlas.org/#:~:text=Diabetes around the world in 2021%3A,- and middle-income countries

Jiang, X., Xu, Q., Zhang, A., Liu, Y., Li, Z., Tang, H., Cao, D., & Zhang, D. (2021). Revealing the Hypoglycemic Effects and Mechanism of GABA-Rich Germinated Adzuki Beans on T2DM Mice by Untargeted Serum Metabolomics. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.791191

Jin, Z., & Korol, S. V. (2023). GABA signalling in human pancreatic islets. Frontiers in Endocrinology, 14, 105911, 1–7. https://doi.org/10.3389/fendo.2023.1059110

Lagunas-Rangel, F. A., Koshelev, D., Nedorubov, A., Kosheleva, L., Trukhan, V., Rabinovitch, A., Schiöth, H. B., & Levit, S. (2022). Triple drug therapy with GABA, sitagliptin, and omeprazole prevents type 1 diabetes onset and promotes its reversal in non-obese diabetic mice. Frontiers in Endocrinology, 13. https://doi.org/10.3389/fendo.2022.1028114

Liu, W., Son, D. O., Lau, H. K., Zhou, Y., Prud’homme, G. J., Jin, T., & Wang, Q. (2017). Combined Oral Administration of GABA and DPP-4 Inhibitor Prevents Beta Cell Damage and Promotes Beta Cell Regeneration in Mice. Frontiers in Pharmacology, 8, 362, 1–10. https://doi.org/10.3389/fphar.2017.00362

Martin, A., Mick, G. J., Choat, H. M., Lunsford, A. A., Tse, H. M., McGwin, G. G., & McCormick, K. L. (2022). A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes. Nature Communications, 13(1), 1–10. https://doi.org/10.1038/s41467-022-35544-3

Martin, P., Massol, J., Pichat, P., & Puech, A. J. (1998). Decreased central GABA B receptor binding sites in diabetic rats. Neuropsychobiology, 19(3), 146–148. https://doi.org/10.1159/000118451

Menegaz, D., Hagan, D. W., Almaça, J., Cianciaruso, C., Rodriguez-Diaz, R., Molina, J., Dolan, R. M., Becker, M. W., Schwalie, P. C., Nano, R., Lebreton, F., Kang, C., Sah, R., Gaisano, H. Y., Berggren, P. O., Baekkeskov, S., Caicedo, A., & Phelps, E. A. (2019). Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell. Nature Metabolism, 1(11), 1110–1126. https://doi.org/10.1038/s42255-019-0135-7

Ngo, D. H., & Vo, T. S. (2019). An updated review on pharmaceutical properties of gamma-aminobutyric acid. Molecules, 24(15), 1–23. https://doi.org/10.3390/molecules24152678

Nikmaram, N., Dar, B. N., Roohinejad, S., Koubaa, M., Barba, F. J., Greiner, R., & Johnson, S. K. (2017). Recent advances in γ-aminobutyric acid (GABA) properties in pulses: an overview. Journal of the Science of Food and Agriculture, 97(9), 2681–2689. https://doi.org/10.1002/jsfa.8283

O’Kell, A. L., Wasserfall, C., Guingab-Cagmat, J., Webb-Roberston, B.-J. M., Atkinson, M. A., & Garrett, T. J. (2021). Targeted metabolomic analysis identifies increased serum levels of GABA and branched chain amino acids in canine diabetes. Metabolomics, 17(11), 100. https://doi.org/10.1007/s11306-021-01850-y

Rabinovitch, A., Koshelev, D., Lagunas-Rangel, F. A., Kosheleva, L., Gavra, T., Schiöth, H. B., & Levit, S. (2023). Efficacy of combination therapy with GABA, a DPP-4i and a PPI as an adjunct to insulin therapy in patients with type 1 diabetes. Frontiers in Endocrinology, 14. https://doi.org/10.3389/fendo.2023.1171886

Rezazadeh, H., Sharifi, M. R., Sharifi, M., & Soltani, N. (2021). Gamma-aminobutyric acid attenuates insulin resistance in type 2 diabetic patients and reduces the risk of insulin resistance in their offspring. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 138(2021), 1–13. https://doi.org/10.1016/j.biopha.2021.111440

Sallard, E., Letourneur, D., & Legendre, P. (2021). Electrophysiology of ionotropic GABA receptors. Cellular and Molecular Life Sciences, 78(13), 5341–5370. https://doi.org/10.1007/s00018-021-03846-2

Sarnobat, D., Charlotte Moffett, R., Flatt, P. R., Irwin, N., & Tarasov, A. I. (2022). GABA and insulin but not nicotinamide augment α- to β-cell transdifferentiation in insulin-deficient diabetic mice. Biochemical Pharmacology, 199, 115019. https://doi.org/10.1016/J.BCP.2022.115019

Serrano-Regal, M. P., Bayón-Cordero, L., Ordaz, R. P., Garay, E., Limon, A., Arellano, R. O., Matute, C., & Sánchez-Gómez, M. V. (2020). Expression and Function of GABA Receptors in Myelinating Cells. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/fncel.2020.00256

Shaye, H., Stauch, B., Gati, C., & Cherezov, V. (2021). Molecular mechanisms of metabotropic GABAB receptor function. Science Advances, 7(22), 3362. https://doi.org/10.1126/sciadv.abg3362

Shen, C., Mao, C., Xu, C., Jin, N., Zhang, H., Shen, D. D., Shen, Q., Wang, X., Hou, T., Chen, Z., Rondard, P., Pin, J. P., Zhang, Y., & Liu, J. (2021). Structural basis of GABAB receptor-Gi protein coupling. Nature, 594(7864), 594–598. https://doi.org/10.1038/s41586-021-03507-1

Sohrabipour, S., Sharifi, M. R., Talebi, A., & Soltani, N. (2018). GABA dramatically improves glucose tolerance in streptozotocin-induced diabetic rats fed with high-fat diet. European Journal of Pharmacology, 826, 75–84. https://doi.org/10.1016/J.EJPHAR.2018.01.047

Soltani, N., Qiu, H., Aleksic, M., Glinka, Y., Zhao, F., Liu, R., Li, Y., Zhang, N., Chakrabarti, R., Ng, T., Jin, T., Zhang, H., Lu, W. Y., Feng, Z. P., Prud’homme, G. J., & Wang, Q. (2011). GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. In Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1102715108

Taneera, J., Jin, Z., Jin, Y., Muhammed, S. J., Zhang, E., Lang, S., Salehi, A., Korsgren, O., Renström, E., Groop, L., & Birnir, B. (2012). γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes. Diabetologia, 55(7), 1985–1994. https://doi.org/10.1007/s00125-012-2548-7

Terunuma, M. (2018). Diversity of structure and function of GABAB receptors: a complexity of GABAB-mediated signaling. In Proceedings of the Japan Academy. Series B, Physical and Biological Sciences. https://doi.org/10.2183/pjab.94.026

Thielen, J. W., Gancheva, S., Hong, D., Rankouhi, S. R., Chen, B., Apostolopoulou, M., Anadol-Schmitz, E., Roden, M., Norris, D. G., & Tendolkar, I. (2019). Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction. Human Brain Mapping, 40(14), 4287–4295. https://doi.org/10.1002/hbm.24702

Tian, J., & Kaufman, D. L. (2023). The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19. Biomedicines, 11(2), 254. https://doi.org/10.3390/biomedicines11020254

Untereiner, A., Abdo, S., Bhattacharjee, A., Gohil, H., Pourasgari, F., Ibeh, N., Lai, M., Batchuluun, B., Wong, A., Khuu, N., Liu, Y., Rijjal, D. A., Winegarden, N., Virtanen, C., Orser, B. A., Cabrera, O., Varga, G., Rocheleau, J., Dai, F. F., & Wheeler, M. B. (2019). GABA promotes β-cell proliferation, but does not overcome impaired glucose homeostasis associated with diet-induced obesity. FASEB Journal, 33(3), 3968–3984. https://doi.org/10.1096/fj.201801397R

World Health Organization, W. (2020). The top 10 causes of death. Retrieved from https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death

Yeap, S. K., Mohd Ali, N., Mohd Yusof, H., Alitheen, N. B., Beh, B. K., Ho, W. Y., Koh, S. P., & Long, K. (2012). Antihyperglycemic effects of fermented and nonfermented mung bean extracts on alloxan-induced-diabetic mice. Journal of Biomedicine & Biotechnology, 28, 1–17. https://doi.org/10.1155/2012/285430

Zhang, A., Jiang, X., Ge, Y., Xu, Q., Li, Z., Tang, H., Cao, D., & Zhang, D. (2022). The Effects of GABA-Rich Adzuki Beans on Glycolipid Metabolism, as Well as Intestinal Flora. In Type 2 Diabetic Mice. Frontiers in Nutrition, 9. https://doi.org/10.3389/fnut.2022.849529

Zhu, Y., Devi, S., Kumar, M., Dahiya, R. S., & Tarkeshwer. (2021). Evaluation of Gamma Amino Butyric Acid (GABA) and Glibenclamide Combination Therapy in Streptozotocin Induced Diabetes. Endocrine, Metabolic & Immune Disorders - Drug Targets, 21(11), 2005–2016. https://doi.org/10.2174/1871530320666201208110945

Author Biographies

Meti Indrowati, Universitas Sebelas Maret

Harlita, Universitas Sebelas Maret

Umi Fatmawati, Universitas Sebelas Maret

Joko Ariyanto, Universitas Sebelas Maret

Estu Retnaningtyas, Universitas Sebelas Maret

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