bhumica kiran,
- Student Department of Biotechnology, Ramaiah university of applied sciences, Mathikere,Bengaluru, Karnataka. India
Abstract
Objective: Diabesity, the amalgamation of diabetes and obesity, presents a significant global health
challenge. This research carefully examines the ways in which plant secondary metabolites influence
glucose regulation in diabetes by means of the PKA/CREB pathway, paying particular attention to
diabesity—the combination of diabetes and obesity. Understanding the complex ways in which these
metabolites affect metabolic health will help to identify new treatment approaches for managing
diabetes and its associated problems. By conducting a thorough analysis, this research aims to provide
essential insights into the creation of focused interventions that will ultimately improve the management
of metabolic disorders in general and the health of the general public by addressing the various
challenges presented by obesity. Methods: The study aimed to evaluate the efficacy of various
phytochemicals against diabetes using computational techniques to target the proteins 4uj1 and 6e99.
Protein structures were validated using PDBsum and BIOVIA Discovery Studio. Molecular docking,
facilitated by PyRx, utilized data from PubChem and molecular structures from Indian medicinal
plants. Ligands were pharmacologically assessed using ADMET filters. This comprehensive approach,
integrating multiple data sources and computational methods, offers deep insights into potential antidiabetic
medications. The use of advanced technologies such as molecular docking and protein
structural validation enhances our understanding of the therapeutic potential of natural compounds in
diabetes management. The results highlight the importance of combining traditional knowledge with
modern scientific techniques to develop effective treatments, suggesting that compounds from Indian
medicinal plants may offer novel strategies for treating diabetes and related metabolic disorders.
Results: Molecular docking experiments identified ginkgolides, nimbin, tetrandrine, emblicanin A, and
ginsenosides as ligands with the lowest binding affinities to the target proteins, indicating their
potential as anti-hyperglycemic agents. Conclusion: Nimbin, due to its low binding affinity for the
proteins 4uj1 and 6e99, shows promise for diabetes therapy through the PKA/CREB pathway. This
finding underscores the significance of nimbin in ongoing diabetes research and clinical trials,
highlighting its potential for developing new treatment strategies.
Keywords: Diabetes; Diabetes mellitus; Type 2 DM; Type 1 DM; Obesity; PKA/CREB pathway; Anti-hyperglycemia
References
- Ahmed AM. History of diabetes mellitus. Saudi Med J. 2002 Apr;23(4):373-8. PMID: 11953758.
- Kaul K, Tarr JM, Ahmad SI, Kohner EM, Chibber R. Introduction to diabetes mellitus. Adv Exp Med Biol. 2012;771:1-11. doi: 10.1007/978-1-4614-5441-0_1. PMID: 23393665.
- Brewer CJ, Balen AH. The adverse effects of obesity on conception and implantation. Reproduction. 2010 Sep;140(3):347-64. doi: 10.1530/REP-09-0568. Epub 2010 Apr 15. PMID: 20395425.
- Farag YM, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant. 2011 Jan;26(1):28-35. doi: 10.1093/ndt/gfq576. Epub 2010 Nov 2. PMID: 21045078.
- Colagiuri S. Diabesity: therapeutic options. Diabetes Obes Metab. 2010 Jun;12(6):463-73. doi: 10.1111/j.1463-1326.2009.01182.x. PMID: 20518802.
- Benchoula K, Parhar IS, Madhavan P, Hwa WE. CREB nuclear transcription activity as a targeting factor in the treatment of diabetes and diabetes complications. Biochem Pharmacol. 2021 Jun;188:114531. doi: 10.1016/j.bcp.2021.114531. Epub 2021 Mar 25. PMID: 33773975.
- Jocken JW, Roepstorff C, Goossens GH, van der Baan P, van Baak M, Saris WH, Kiens B, Blaak EE. Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation. Diabetes. 2008 Jul;57(7):1834-41. doi: 10.2337/db07-0857. Epub 2008 Apr 8. PMID: 18398140; PMCID: PMC2453623.
- London E, Bloyd M, Stratakis CA. PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies. J Endocrinol. 2020 Sep;246(3):R51-R64. doi: 10.1530/JOE-20-0035. PMID: 32485681; PMCID: PMC7385994.
- Mantovani G, Bondioni S, Alberti L, Gilardini L, Invitti C, Corbetta S, Zappa MA, Ferrero S, Lania AG, Bosari S, Beck-Peccoz P, Spada A. Protein kinase A regulatory subunits in human adipose tissue: decreased R2B expression and activity in adipocytes from obese subjects. Diabetes. 2009 Mar;58(3):620-6. doi: 10.2337/db08-0585. Epub 2008 Dec 18. PMID: 19095761; PMCID: PMC2646060.
- Marrades MP, González-Muniesa P, Martínez JA, Moreno-Aliaga MJ. A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity. Obes Facts. 2010 Oct;3(5):312-8. doi: 10.1159/000321451. Epub 2010 Oct 15. PMID: 20975297; PMCID: PMC6452131.
- Boles A, Kandimalla R, Reddy PH. Dynamics of diabetes and obesity: Epidemiological perspective. Biochim Biophys Acta Mol Basis Dis. 2017 May;1863(5):1026-1036. doi: 10.1016/j.bbadis.2017.01.016. Epub 2017 Jan 24. PMID: 28130199; PMCID: PMC5429876.
- Maggio CA, Pi-Sunyer FX. The prevention and treatment of obesity. Application to type 2 diabetes. Diabetes Care. 1997 Nov;20(11):1744-66. doi: 10.2337/diacare.20.11.1744. PMID: 9353619.
- Williams KV, Kelley DE. Metabolic consequences of weight loss on glucose metabolism and insulin action in type 2 diabetes. Diabetes Obes Metab. 2000 Jun;2(3):121-9. doi: 10.1046/j.1463-1326.2000.00049.x. PMID: 11220547.
- Bahmani, M., Golshahi, H., Saki, K., Rafieian-Kopaei, M., Delfan, B., & Mohammadi, T. (2014). Medicinal plants and secondary metabolites for diabetes mellitus control. Asian Pacific Journal of Tropical Disease, 4, S687–S692. doi:10.1016/s2222-1808(14)60708-8.
Volume | |
Received | April 1, 2024 |
Accepted | May 23, 2024 |
Published | August 24, 2024 |