Antidiabetic Research: A Review of Drosophila melanogaster Models, Molecular Mechanisms, and Experimental Protocols
DOI:
https://doi.org/10.63561/jabs.v2i3.933Keywords:
Drosophila melanogaster, Diabetes modelling, Antidiabetic plants, Culturing of fruit flyAbstract
Drosophila melanogaster has emerged as a valuable model organism for investigating metabolic disorders, particularly in the realm of diabetes research. It effectively replicates the intricate nature of human diabetes, making it an ideal subject for creating diabetes models. Its acceptance as an experimental model stems from several factors, including the simplicity of genetic manipulation, cost-effectiveness, and time efficiency. The conservation of insulin signalling and metabolic pathways between Drosophila melanogaster and mammals further underscores its relevance in elucidating human diabetes mechanisms. Studies have shown that Drosophila are used as an experimental model to show the antidiabetic activity of numerous plants such as Cyperus rotundus L. Kombucha, Potentilla discolor Bunge, Spondias mombin (Linn), Soy isoflavone and Atriplex halimus. Successful research outcomes with Drosophila melanogaster depend largely on maintaining optimal culture conditions and employing techniques that minimize stress and injury to the flies. This review examines the significance of Drosophila melanogaster in antidiabetic research, encompassing the underlying molecular mechanisms, experimental protocols, applications in drug screening and the challenges associated with utilizing this model organism.
References
Alfa, R.W., & Kim S. K. (2016). Using Drosophila to discover mechanisms underlying type 2 diabetes. Disease Models & Mechanisms. 9(4):365–376. doi: 10.1242/dmm.023887. http://dx.doi.org/10.1242/dmm.023887. [DOI] [PMC free article] [PubMed] [Google Scholar] DOI: https://doi.org/10.1242/dmm.023887
Ashburner, M., Golic, K. G., & Hawley, R. S. (2005). Drosophila: A Laboratory Handbook (2nd ed.). Cold Spring Harbor Laboratory Press.
Ashrafi, K., Ali, S., Husain, T., & Khan, S. (2014). "The Role of Drosophila in Antidiabetic Research: A Model System for the Identification of Therapeutic Compounds." Journal of Diabetes Research, 2014, 1-10.
Bai, Y., Li, K., Shao, J., Juo, Q. & Jin, L.H. (2018). Flos Chrysanthemi indici extract improves a high-sucrose diet-induced metabolic disorder in Drosophila. Exp Ther Med 16: 2564e2572. DOI: https://doi.org/10.3892/etm.2018.6470
Bauer, A., & Weber, C. (2008). "Drosophila melanogaster: A Model Organism for Behavioral and Functional Neuroscience." Journal of Visualized Experiments, 22, e1056. https://doi.org/10.3791/1056
Catalani, E., Silvestri, F., Bongiorni, S., Taddei, A.R., Fanelli, G., Rinalducci, S., De Palma, C., Perrotta, C., Prantera, G., & Cervia, D (2021). Retinal damage in a new model of hyperglycemia induced by high-sucrose diets. Pharmacol. Res. , 166, 105488. [Google Scholar] [CrossRef] DOI: https://doi.org/10.1016/j.phrs.2021.105488
Dechakhamphu, A., Wongchum, N., Chumroenphat, T., Tanomtong, A., Pinlaor, S., & Siriamornpun, S (2023). In Vitro and In Vivo Evaluation for Antioxidant and Anti-Diabetic Properties of Cyperus rotundus L. Kombucha. Foods, 12, 4059. https://doi.org/10.3390/ foods12224059 DOI: https://doi.org/10.3390/foods12224059
Geminard, C., Rulifson, E. J., & Leopold, P. (2009). "Insulin Regulation of Glucose Metabolism in Drosophila." Molecular Cell Biology, 29(17), 4734-4746.
Graham, P & Pick, L (2017). Drosophila as a Model for Diabetes and Diseases of Insulin Resistance. Curr Top Dev Biol. 121:397-419. doi: 10.1016/bs.ctdb.2016.07.011. DOI: https://doi.org/10.1016/bs.ctdb.2016.07.011
Greenspan, R. J. (2004). Fly Pushing: The Theory and Practice of Drosophila Genetics. Cold Spring Harbor Laboratory Press.
Grönke, S.; Clarke, D.F.; Broughton, S.; Andrews, T.D.; Partridge, L (2010). Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 6, e1000857. [Google Scholar] [CrossRef] [Green Version DOI: https://doi.org/10.1371/journal.pgen.1000857
Günther, I., Rimbach, G., Nevermann, S., Neuhauser, C., Stadlbauer, V., Schwarzinger, B., Schwarzinger, C., Ipharraguerre, IR., Weghuber, J &Lüersen K (2021) Avens Root (Geum Urbanum L.) Extract Discovered by Target-Based Screening Exhibits Antidiabetic Activity in the Hen’s Egg Test Model and Drosophila melanogaster. Front. Pharmacol. 12:794404. doi: 10.3389/fphar.2021.794404 DOI: https://doi.org/10.3389/fphar.2021.794404
Hanaa, E., Montaser, O., El-Aasr, M & Meshrif, W. S (2021). Potential anti-diabetic effect of certain plant extracts from the Egyptian flora on type II diabetes using Drosophila melanogaster as an animal model. International Journal of Cancer and Biomedical Research Vol. 5(4): 121-133. DOI: 10.21608/jcbr.2021.90207.1225 DOI: https://doi.org/10.21608/jcbr.2021.90207.1225
Herranz, H, & Cohen SM (2017). Drosophila as a Model to Study the Link between Metabolism and Cancer. J Dev Biol. 5:15. doi: 10.3390/jdb5040015 DOI: https://doi.org/10.3390/jdb5040015
Honegger, B., Galic, M., & Kohler, K. (2008). "The Insulin Signaling Pathway and Its Role in Drosophila." Developmental Dynamics, 237(10), 2892-2899.
Karthikeyan, M., Balasubramanian, T., & Kumar, P (2016) In-vivo Animal Models and In-vitro Techniques for Screening Antidiabetic Activity. J Develop Drugs 5: 153. doi:10.4172/2329-6631.1000153 DOI: https://doi.org/10.4172/2329-6631.1000153
Khan, T. A & Sievenpiper, J. L (2016). Controversies about sugars: results from systematic reviews and meta-analyses on obesity, cardiometabolic disease and diabetes. Eur J Nutr, 55: S25e S43. DOI: https://doi.org/10.1007/s00394-016-1345-3
Khan, M.A.B., Hashim, M.J., King, J.K., Govender, R.D., Mustafa, H & Al Kaabi, J (2020). Epidemiology of Type 2 Diabetes–Global Burden of Disease and Forecasted Trends. J. Epidemiol. Glob. Health, 10, 107–111. [CrossRef] [PubMed] DOI: https://doi.org/10.2991/jegh.k.191028.001
Kumar, J., Srivastava, V., & Najmi, A. K. (2016). "Drosophila as a Model Organism for Diabetes Research." Biotechnology Advances, 34(7), 1160-1174.
Li, Y., Wu, F., Zhang, J., Xu, Y., Chang, H., Yu, Y., Jiang, C., Gao, X., Liu, H., Chen, Z., Wu, C., Li, J. A (2024). Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila.Drug Des Devel Ther. 18:747-766 https://doi.org/10.2147/DDDT.S439876 DOI: https://doi.org/10.2147/DDDT.S439876
Liguori, F., Mascolo, E., & Vernì, F. (2021). The Genetics of Diabetes: What We Can Learn from Drosophila. International Journal of Molecular Sciences, 22(20), 11295. https://doi.org/10.3390/ijms222011295 DOI: https://doi.org/10.3390/ijms222011295
Liu, Z., Huang, J., Li, Y., & Chen, L. (2020). "Antidiabetic Effects of Plant Extracts in Drosophila Models of Type 2 Diabetes." Journal of Ethnopharmacology, 254, 112692. https://doi.org/10.1016/j.jep.2019.112692
Lopez-Ortiz, C., Gracia-Rodriguez, C., Belcher, S., Flores-Iga, G., Das, A., Nimmakayala, P., Balagurusamy, N & Reddy, U.K (2023). Drosophila melanogaster as a Translational Model System to Explore the Impact of Phytochemicals on Human Health. Int. J. Mol. Sci, 24, 13365. https://doi.org/10.3390/ ijms241713365 DOI: https://doi.org/10.3390/ijms241713365
Lüersen, K., Fischer, A., Bauer, I., Huebbe, P., Uekaji, Y., Chikamoto, K., Nakata, D., Hiramatsu, N., Terao, K., & Rimbach, G (2023). Soy Extract, Rich in Hydroxylated Isoflavones, Exhibits Antidiabetic Properties In Vitro and in Drosophila melanogaster In Vivo. Nutrients, 15, 1392. https://doi.org/10.3390/ nu15061392 DOI: https://doi.org/10.3390/nu15061392
McEwen, R. J., & Gould, A. P. (2016). "Working with Drosophila: A Laboratory Manual." Oxford University Press.
Miao, Y., Chen, R., Wang, X., Zhang, J., Tang, W., Zhang, Z., Liu, Y & Xu, Q (2022) Drosophila melanogaster diabetes models and its usage in the research of anti-diabetes management with traditional Chinese medicines. Front. Med. 9:953490. doi: 10.3389/fmed.2022.953490 DOI: https://doi.org/10.3389/fmed.2022.953490
Montaser, O., El-Aasr, M., Tawfik, H.O., Meshrif, W. S., & Elbrense, H (2024). Drosophila melanogaster as a model organism for diabetes II treatment by the ethyl acetate fraction of Atriplex halimus L. J Exp Zool A Ecol Integr Physiol. 341(6):702-716. doi: 10.1002/jez.2812. Epub 2024 Apr 16. PMID: 38623920. DOI: https://doi.org/10.1002/jez.2812
Morris, S.N.S., Coogan, C., Chamseddin, K., Fernandez-Kim, S.O., Kolli, S., Keller, J.N., & Bauer, J.H (2012). Development of diet-induced insulin resistance in adult Drosophila melanogaster. Biochim. Biophys. Acta. BBA-Mol. Basis. Dis. 1822, 1230–1237. [CrossRef] DOI: https://doi.org/10.1016/j.bbadis.2012.04.012
Murillo-Maldonado, J. M & Riesgo-Escovar, J. R (2017). Development and diabetes on the fly. Mechanisms of Development, 144: 150-155. DOI: https://doi.org/10.1016/j.mod.2016.09.004
Na, J., Musselman, L. P., Pendse, J., Baranski, T. J., Bodmer, R., Ocorr, K., Cagan, R. A (2013) Drosophila model of high sugar diet-induced cardiomyopathy. PLoS Genetics;9 (1):e1003175.doi:10.1371/journal.pgen.1003175.http://dx.doi.org/10.1371/journal.pgen.1003175. [DOI] [PMC free article] [PubMed] [Google Scholar] DOI: https://doi.org/10.1371/journal.pgen.1003175
Nässel, D.R., Kubrak, O.I., Liu, Y., Luo, J., & Lushchak, O.V (2013). Factors that regulate insulin producing cells and their output in Drosophila. Front. Physiol. 4, 252. [Google Scholar] [CrossRef] DOI: https://doi.org/10.3389/fphys.2013.00252
Ogienko, A.A., Omelina, E.S., Bylino, O.V., Batin, M.A., Georgiev, P.G., & Pindyurin, A.V (2022). Drosophila as a Model Organism to Study Basic Mechanisms of Longevity. Int J Mol Sci. 24;23(19):11244. doi: 10.3390/ijms231911244. PMID: 36232546; PMCID: PMC9569508. DOI: https://doi.org/10.3390/ijms231911244
Omale, S., J.C. Aguiyi., O.G. Adekunle., T.O. Johnson., S.O. Ochala., M.A. Etuh & M.C. Eze (2021). Evaluation of the antidiabetic effects of the stem bark extract of Parinari curatellifolia (Planch. ex Benth.) in Drosophila melanogaster. J. Pharmacol. Toxicol., 16: 9-21 DOI: https://doi.org/10.3923/jpt.2021.9.21
Omoboyowa, D. A., Agoi, M.D., Shodehinde, S.A., Saibu, O.A., & Saliu, J. A (2023). Antidiabetes study of Spondias mombin (Linn) stem bark fractions in high sucrose diet-induced diabetes in Drosophila melanogaster. J Taibah Univ Med Sc. 18(4):663e675 DOI: https://doi.org/10.1016/j.jtumed.2023.01.011
Palanker, L., Fink, J.L.; Narzinski, K., Ramachandran, P.V., Sukumar Hathiramani, S., Cagan, R.L., & Baranski, T.J (2011). A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. Dis. Model. Mech. 4, 842–849. [CrossRef] [PubMed] DOI: https://doi.org/10.1242/dmm.007948
Partridge, L., Alic, N., Bjedov, I., & Piper, M.D (2011). Ageing in Drosophila: The role of the insulin/Igf and TOR signalling network. Exp. Gerontol. 46, 376–381. [CrossRef] [PubMed] DOI: https://doi.org/10.1016/j.exger.2010.09.003
Rani, L., Saini, S., Shukla, N., Chowdhuri, D.K., & Gautam, N.K. (2020). High sucrose diet induces morphological, structural and functional impairments in the renal tubules of Drosophila melanogaster: A model for studying type-2 diabetes mediated renal tubular dysfunction. Insect Biochem. Mol. Biol. 125, 103441. [Google Scholar] [CrossRef] DOI: https://doi.org/10.1016/j.ibmb.2020.103441
Sarkar, A., & Whitley, P. (2014). "Handling and Maintenance of Drosophila melanogaster." Methods in Molecular Biology, 1159, 23-31. https://doi.org/10.1007/978-1-4939-0801-1_3
Slonim, D., Wang, Y., Harrington, M., & Scott, M. (2009). "Drosophila melanogaster: A Model for Studying Insulin Signaling and Diabetes." Developmental Dynamics, 238(6), 1342-1352.
Sullivan, W., Ashburner, M., & Hawley, R. S. (2000). Drosophila Protocols. Cold Spring Harbor Laboratory Press.
Teleman, A. A. (2010). Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochemical Journal, 425(1): 13-26. DOI: https://doi.org/10.1042/BJ20091181
Wang, M., Mao, H., Chen, J., Qi, L & Wang J (2022), Ameliorative effect of bayberry leaves proanthocyanidins on high sugar diet induced Drosophila melanogaster. Front. Pharmacol. 13:1008580. doi: 10.3389/fphar.2022.1008580 DOI: https://doi.org/10.3389/fphar.2022.1008580
Ying, L., Junlin, W., Yidong, X., Qinghao, M., Mengdi, W., Yanfang, S., Yaodong, M., & Yiwen, W (2023). The water extract of Potentilla discolor Bunge (PDW) ameliorates high-sugar diet-induced type II diabetes model in Drosophila melanogaster via JAK/STAT signaling. Journal of Ethnopharmacology, Volume 316, 116760, ISSN 0378-8741, https://doi.org/10.1016/j.jep.2023.116760. DOI: https://doi.org/10.1016/j.jep.2023.116760
Zaki, S., Chaithra, M. L., Bansal, S., Latha, V., Bajpai, M., Malathi, R & Sibi, G (2021). In vitro anti-inflammatory, anti-diabetic and antioxidant potential of Cissus quadrangularis along with its orexigenic activity in Drosophila melanogaster. Journal of Applied and Natural Science, 13(3), 962 - 969. https:// doi.org/10.31018/jans.v13i3.2835 DOI: https://doi.org/10.31018/jans.v13i3.2835
Zhang, Y., Rohatgi, N., & Kim, S. (2009). "Drosophila Models of Type 2 Diabetes." Diabetes Research and Clinical Practice, 85(3), 181-185. DOI: https://doi.org/10.1016/S0168-8227(09)00274-5
Zheng, Y., Ley, S. H., & Hu, F. B. (2018). Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Reviews Endocrinology, 14(2), 88-98. DOI: https://doi.org/10.1038/nrendo.2017.151