Determination of molecular mechanisms of development and course of experimental diabetes mellitus in Wistar rats

Authors

DOI:

https://doi.org/10.14739/2409-2932.2023.2.281209

Keywords:

Wistar rats, pancreas, genes Nkx2-1, Pik3r1, Slc14a2

Abstract

The development and progression of diabetes involves several molecular mechanisms, in particular: insulin resistance, dysfunction of beta cells, inflammatory processes. These mechanisms can disrupt insulin signaling pathways, contribute to beta-cell apoptosis, and are not necessarily dependent on the intervention of cytokines and chemokines. Additionally, genetics play a role, as some forms of diabetes are caused by genetic mutations affecting insulin production or sensitivity. The molecular mechanisms underlying the development and progression of diabetes are complex and encompass various aspects of the body’s physiology and biochemistry. Understanding these mechanisms is crucial for the development of effective methods for treating and preventing diabetes.

The aim of the work is analysis of the expression of genes, related to diabetes in pancreatic tissue samples of Wistar rats.

Materials and methods. The polymerase chain reaction method with real-time reverse transcription was used to analyze gene expression using the RTI Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany), where the pancreas was the object of research in experimental animals.

Results. RTI Profiler™ PCR Array Rat Diabetes profiles the expression of 84 genes, associated with the onset, development, and progression of diabetes. The panel contains genes that contribute to obesity, insulin resistance, early-onset diabetes, and its late complications. These genes are represented by functional categories: receptors, transporters, and channels; nuclear receptors; metabolic enzymes; secretion factors; signal transduction proteins; transcription factors.

According to the PCR results of the study of the control group of animals and animals with experimental diabetes, we established the activity of the Nkx2-1 genes; Pik3r1; Slc14a2 with high expression compared to control animals.

Conclusions. The Nkx2-1 gene has been implicated in the pathogenesis of diabetes, as evidenced by its high expression activity compared to the control group of animals. Additionally, the Pik3r1 protein shows elevated expression levels in the group of animals with experimental diabetes. These changes are believed to be part of a compensatory mechanism aimed at preserving the cellular function of the pancreatic endocrine system. Furthermore, the observed increase in Slc14a2 protein expression likely indicates the onset of late complications associated with kidney pathology in the course of diabetes.

Author Biography

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

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

References

Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.), 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262

Takematsu, E., Spencer, A., Auster, J., Chen, P. C., Graham, A., Martin, P., & Baker, A. B. (2020). Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes. PloS one, 15(2), e0225267. https://doi.org/10.1371/journal.pone.0225267

Coon, E. A., Ahlskog, J. E., Patterson, M. C., Niu, Z., & Milone, M. (2016). Expanding Phenotypic Spectrum of NKX2-1-Related Disorders-Mitochondrial and Immunologic Dysfunction. JAMA neurology, 73(2), 237-238. https://doi.org/10.1001/jamaneurol.2015.2976

Sivitz, W. I., & Yorek, M. A. (2010). Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxidants & redox signaling, 12(4), 537-577. https://doi.org/10.1089/ars.2009.2531

Rojek, A., & Niedziela, M. (2010). Insulin receptor and its relationship with different forms of insulin resistance. Advances in Cell Biology, 2010, 58-89. https://doi.org/10.2478/v10052-010-0004-8

Honardoost, M., Sarookhani, M. R., Arefian, E., & Soleimani, M. (2014). Insulin resistance associated genes and miRNAs. Applied biochemistry and biotechnology, 174(1), 63-80. https://doi.org/10.1007/s12010-014-1014-z

Andrade, V. P., Morrogh, M., Qin, L. X., Olvera, N., Giri, D., Muhsen, S., Sakr, R. A., Schizas, M., Ng, C. K., Arroyo, C. D., Brogi, E., Viale, A., Morrow, M., Reis-Filho, J. S., & King, T. A. (2015). Gene expression profiling of lobular carcinoma in situ reveals candidate precursor genes for invasion. Molecular oncology, 9(4), 772-782. https://doi.org/10.1016/j.molonc.2014.12.005

Knoll, K. E., Pietrusz, J. L., & Liang, M. (2005). Tissue-specific transcriptome responses in rats with early streptozotocin-induced diabetes. Physiological genomics, 21(2), 222-229. https://doi.org/10.1152/physiolgenomics.00231.2004

Yang, L., Brozovic, S., Xu, J., Long, Y., Kralik, P. M., Waigel, S., Zacharias, W., Zheng, S., & Epstein, P. N. (2011). Inflammatory gene expression in OVE26 diabetic kidney during the development of nephropathy. Nephron. Experimental nephrology, 119(1), e8-e20. https://doi.org/10.1159/000324407

Zheng, S., Huang, Y., Yang, L., Chen, T., Xu, J., & Epstein, P. N. (2011). Uninephrectomy of diabetic OVE26 mice greatly accelerates albuminuria, fibrosis, inflammatory cell infiltration and changes in gene expression. Nephron. Experimental nephrology, 119(1), e21-e32. https://doi.org/10.1159/000327586

Jaffa, M. A., Kobeissy, F., Al Hariri, M., Chalhoub, H., Eid, A., Ziyadeh, F. N., & Jaffa, A. A. (2012). Global renal gene expression profiling analysis in B2-kinin receptor null mice: impact of diabetes. PloS one, 7(9), e44714. https://doi.org/10.1371/journal.pone.0044714

Komers, R., Xu, B., Fu, Y., McClelland, A., Kantharidis, P., Mittal, A., Cohen, H. T., & Cohen, D. M. (2014). Transcriptome-based analysis of kidney gene expression changes associated with diabetes in OVE26 mice, in the presence and absence of losartan treatment. PloS one, 9(5), e96987. https://doi.org/10.1371/journal.pone.0096987

Published

2023-07-03

How to Cite

1.
Ivanenko TV. Determination of molecular mechanisms of development and course of experimental diabetes mellitus in Wistar rats. Current issues in pharmacy and medicine: science and practice [Internet]. 2023Jul.3 [cited 2024Apr.14];16(2):154-7. Available from: http://pharmed.zsmu.edu.ua/article/view/281209

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Section

Original research