Identification and analysis of the expression of genes, involved in insulin signals transmission in the development of experimental type 2 diabetes mellitus

Authors

DOI:

https://doi.org/10.14739/2409-2932.2024.1.297509

Keywords:

pancreas, diabetes mellitus, genes, insulin, laboratory diagnostics

Abstract

Type 2 diabetes mellitus is a significant concern due to its high prevalence and impact on global health. Ongoing scientific research aims to enhance our understanding of the mechanisms involved in the development and progression of diabetes and devise effective strategies for its treatment. This involves the development of new pharmacological treatments, including novel antidiabetic drugs, and the exploration of individualized approaches to therapy.

The mechanisms underlying type 2 diabetes are intricate, involving various aspects of physiology and biochemistry. Gaining insight into the development and progression of type 2 diabetes mellitus through modern laboratory diagnostic methods is crucial for the development of effective treatment and prevention strategies for diabetes.

The aim of the study is to identify and analyze a panel of genes, involved in insulin signals transmission in the development of experimental type 2 diabetes mellitus.

Materials and methods. The analysis of gene expression involved in insulin signal transmission was conducted using real-time reverse transcription-polymerase chain reaction (RT-qPCR) on the CFX-96 Touch™ system (Bio-Rad, USA). The RT2Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany) was employed for this purpose.

Results. Based on the study results, the activity of the genes involved in insulin signal transmission can be categorized as follows: genes with low expression compared to the control group of animals, where ∆∆Ct <30 (Akt2, Mapk14, Pik3r1); genes in which no significant changes were detected in the samples compared to the control group (Irs1, Irs2, Pik3cd); no genes with high expression were observed compared to the control group.

Conclusions. In the development of experimental type 2 diabetes mellitus, genes involved in insulin signal transmission (Akt2, Mapk14, Pik3r1) exhibited significantly low expression levels (Akt2 – 2.9, Mapk14 – 5.01, Pik3r1 – 8.87) where ∆∆Ct <30, compared to the control group of animals. Conversely, no significant changes were observed in the expression of genes Irs1, Irs2, Pik3cd, also involved in insulin signal transmission, during the development of experimental type 2 diabetes mellitus, compared to the control group of experimental animals.

Author Biographies

T. V. Ivanenko, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, Associate Professor of the Department of Pathological Physiology with Course of Normal Physiology

A. V. Vynokurova, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, Postgraduate student of the Department of Clinical Laboratory Diagnostics

References

Ahmad A, Lim LL, Morieri ML, Tam CH, Cheng F, Chikowore T, et al. Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis. Commun Med (Lond). 2024;4(1):11. doi: https://doi.org/10.1038/s43856-023-00429-z

Buso G, Aboyans V, Mazzolai L. Lower extremity artery disease in patients with type 2 diabetes. Eur J Prev Cardiol. 2019;26(2_suppl):114-24. doi: https://doi.org/10.1177/2047487319880044

Shali S, Luo L, Yao K, Sun X, Wu H, Zhang S, et al. Triglyceride-glucose index is associated with severe obstructive coronary artery disease and atherosclerotic target lesion failure among young adults. Cardiovasc Diabetol. 2023;22(1):283. doi: https://doi.org/10.1186/s12933-023-02004-1

Schmidt SK, Hemmestad L, MacDonald CS, Langberg H, Valentiner LS. Motivation and Barriers to Maintaining Lifestyle Changes in Patients with Type 2 Diabetes after an Intensive Lifestyle Intervention (The U-TURN Trial): A Longitudinal Qualitative Study. Int J Environ Res Public Health. 2020;17(20):7454. doi: https://doi.org/10.3390/ijerph17207454

García-Chapa EG, Leal-Ugarte E, Peralta-Leal V, Durán-González J, Meza-Espinoza JP. Genetic Epidemiology of Type 2 Diabetes in Mexican Mestizos. Biomed Res Int. 2017;2017:3937893. doi: https://doi.org/10.1155/2017/3937893

Mahajan A, Spracklen CN, Zhang W, Ng MC, Petty LE, Kitajima H, et al. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nat Genet. 2022;54(5):560-72. doi: https://doi.org/10.1038/s41588-022-01058-3

Ferguson D, Finck BN. Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus. Nat Rev Endocrinol. 2021;17(8):484-95. doi: https://doi.org/10.1038/s41574-021-00507-z

Kanaley JA, Colberg SR, Corcoran MH, Malin SK, Rodriguez NR, Crespo CJ, et al. Exercise/Physical Activity in Individuals with Type 2 Diabetes: A Consensus Statement from the American College of Sports Medicine. Med Sci Sports Exerc. 2022;54(2):353-68. doi: https://doi.org/10.1249/MSS.0000000000002800

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8. doi: https://doi.org/10.1006/meth.2001.1262

Xia T, Xu WJ, Hu YN, Luo ZY, He W, Liu CS, et al. Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling. Front Nutr. 2023;9:1012961. doi: https://doi.org/10.3389/fnut.2022.1012961

Meng W, Veluchamy A, Hébert HL, Campbell A, Colhoun HM, Palmer CN. A genome-wide association study suggests that MAPK14 is associated with diabetic foot ulcers. Br J Dermatol. 2017;177(6):1664-70. doi: https://doi.org/10.1111/bjd.15787

Zheng Y, Lang Y, Qi Z, Gao W, Hu X, Li T. PIK3R1, SPNB2, and CRYAB as Potential Biomarkers for Patients with Diabetes and Developing Acute Myocardial Infarction. Int J Endocrinol. 2021;2021:2267736. doi: https://doi.org/10.1155/2021/2267736

Karadoğan AH, Arikoglu H, Göktürk F, İşçioğlu F, İpekçi SH. PIK3R1 gene polymorphisms are associated with type 2 diabetes and related features in the Turkish population. Adv Clin Exp Med. 2018;27(7):921-7. doi: https://doi.org/10.17219/acem/68985

Yiannakouris N, Cooper JA, Shah S, Drenos F, Ireland HA, Stephens JW, et al. IRS1 gene variants, dysglycaemic metabolic changes and type-2 diabetes risk. Nutr Metab Cardiovasc Dis. 2012;22(12):1024-30. doi: https://doi.org/10.1016/j.numecd.2011.05.009

Martínez-Ramírez OC, Salazar-Piña A, Cerón-Ramírez X, Rubio-Lightbourn J, Torres-Romero F, Casas-Avila L, et al. Effect of Inulin Intervention on Metabolic Control and Methylation of INS and IRS1 Genes in Patients with Type 2 Diabetes Mellitus. Nutrients. 2022;14(23):5195. doi: https://doi.org/10.3390/nu14235195

Krause C, Geißler C, Tackenberg H, El Gammal AT, Wolter S, Spranger J, et al. Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes. Diabetologia. 2020;63(10):2182-93. doi: https://doi.org/10.1007/s00125-020-05212-6

Du X, Li X, Chen L, Zhang M, Lei L, Gao W, et al. Hepatic miR-125b inhibits insulin signaling pathway by targeting PIK3CD. J Cell Physiol. 2018;233(8):6052-66. doi: https://doi.org/10.1002/jcp.26442

He FT, Fu XL, Li MH, Fu CY, Chen JZ. USP14 Regulates ATF2/PIK3CD Axis to Promote Microvascular Endothelial Cell Proliferation, Migration, and Angiogenesis in Diabetic Retinopathy. Biochem Genet. 2023;61(5):2076-91. doi: https://doi.org/10.1007/s10528-023-10358-0

Published

2024-02-23

How to Cite

1.
Ivanenko TV, Vynokurova AV. Identification and analysis of the expression of genes, involved in insulin signals transmission in the development of experimental type 2 diabetes mellitus. Current issues in pharmacy and medicine: science and practice [Internet]. 2024Feb.23 [cited 2024Jun.21];17(1):39-43. Available from: http://pharmed.zsmu.edu.ua/article/view/297509