Analysis of molecular mechanisms of the development of experimental diabetes in Wistar rats under conditions of intermittent hypoxia
DOI:
https://doi.org/10.14739/2409-2932.2023.3.287633Keywords:
Wistar rats, diabetes, pancreas, hypoxiaAbstract
There is strong evidence that hypoxic training, within the context of diabetes, constitutes a specialized form of exercise performed under conditions of intermittent hypoxia. This approach holds promise for effectively managing and enhancing diabetes outcomes, as it has the potential to influence metabolism and physiological processes within the body significantly. The key elements of hypoxic training in diabetes encompass activities geared toward activating metabolic pathways, enhancing mitochondrial function, and regulating blood glucose levels. Such interventions can potentially lead to improvements in insulin resistance, a reduction in glycemia, and an overall enhancement of cardiorespiratory function. Hypoxic training achieves these benefits by heightening insulin sensitivity and reducing blood glucose levels, which can be particularly advantageous for individuals with diabetes.
The aim of the work is to determine changes in the expression of genes associated with the course of diabetes under conditions of exposure to intermittent hypoxia in pancreatic tissue samples of Wistar rats.
Materials and methods. Analysis of gene expression was used by the polymerase chain reaction method with reverse transcription in real-time using the RT2 Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany), where the pancreas of experimental animals was studied.
Results. According to the results of the PCR study of animals with experimental diabetes and the influence of hypoxic training on its course, the activity of the studied genes can be divided as follows: genes with low expression compared to the control group of animals, where ∆∆Cт <30 (Ace; Cd28; Ctla4; Dusp4 ; Enpp1; Foxp3; G6pc; Gcgr; Glp1r; Gpd1; Gsk3b; Hmox1; Ide; Ikbkb; Il10; Il6; Ins1; Nfkb1; Nkx2-1; Parp1; Pdx1; Pik3cd; Pik3r1; Ppargc1a; Ptpn1; Rab4a; Retn; Slc14a2 ; Snap25; Sod2; Stx4; Stxbp1; Stxbp2; Tnf; Tnfrsf1a; Tnfrsf1b; Ucp2; Vamp2; Vegfa); genes in which no significant changes were detected in the samples in relation to the control group (Acly; Adra1a; Adrb3; Agt; Akt2; Aqp2; Ccl5; Ccr2; Ceacam1; Cebpa; Dpp4; Fbp1; Foxc2; Foxg1; Gcg; Gck; Hnf1b; Hnf4a ; Icam1; Ifng; Igfbp5; Il12b; Il4r; Inppl1; Irs1; Irs2; Mapk14; Mapk8; Neurod1; Nos3; Nrf1; Nsf; Ppara; Pparg; Pygl; Sell; Serpine1; Slc2a4; Snap23; Srebf1; Stxbp4; Tgfb1; Trib3 ; Vamp3; Vapa); there are no genes with high expression compared to the control group.
Conclusions. The Nkx2-1 genes, Pik3r1, and Slc14a2 in rats subjected to experimental diabetes displayed notably reduced protein expression activity. Hypoxic training demonstrated an impact on mitigating the expression of the Nkx2-1 protein, which suggests that it might affect the mitochondrial muscle respiratory chain, modulate insulin signaling, and potentially rectify molecular deficiencies associated with diabetic nephropathy. Expression of Dpp4 genes, Gck, Ifng, Mapk8, Nsf and Sell in rats with experimental diabetes and the effect of hypoxic training on it were reduced to the level of control (intact) rats. As a result of the normalization of Dpp4 gene expression, Gck, Ifng, Mapk8, Nsf and Sell may be the influence of the effects of hypoxic training on molecular mechanisms of regulation of hormones and signals related to metabolism and the endocrine system, effects on the immune system and inflammatory processes, as well as insulin resistance.
References
Ivanenko, T. V. (2023) Vyznachennia molekuliarnykh mekhanizmiv rozvytku ta perebihu eksperymentalnoho tsukrovoho diabetu v shchuriv linii Vistar [Determination of molecular mechanisms of development and course of experimental diabetes mellitus in Wistar rats]. Current issues in pharmacy and medicine: science and practice, 16(2), 154-157. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2023.2.281209
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262
Serebrovska, T. V. (2020). Indyvidualni osoblyvosti reaktsii na hipoksiiu: suchasni pohliady na mekhanizmy ta prykladni aspekty [Individual features of the response to hypoxia: modern views on mechanisms and applied aspects]. Pathological physiology - health care of Ukraine. Abstracts of reports of the 8th National Congress of Pathophysiologists of Ukraine with international participation (pp. 184-184). Odesa: UkrNDI medytsyny transportu [in Ukrainian].
Mekjavic, I. B., Amon, M., Kölegård, R., Kounalakis, S. N., Simpson, L., Eiken, O., Keramidas, M. E., & Macdonald, I. A. (2016). The Effect of Normobaric Hypoxic Confinement on Metabolism, Gut Hormones, and Body Composition. Frontiers in physiology, 7, 202. https://doi.org/10.3389/fphys.2016.00202
Urdampilleta, A., González-Muniesa, P., Portillo, M. P., & Martínez, J. A. (2012). Usefulness of combining intermittent hypoxia and physical exercise in the treatment of obesity. Journal of physiology and biochemistry, 68(2), 289-304. https://doi.org/10.1007/s13105-011-0115-1
Ye, J., Gao, Z., Yin, J., & He, Q. (2007). Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. American journal of physiology. Endocrinology and metabolism, 293(4), E1118-E1128. https://doi.org/10.1152/ajpendo.00435.2007
Yin, J., Gao, Z., He, Q., Zhou, D., Guo, Z., & Ye, J. (2009). Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. American journal of physiology. Endocrinology and metabolism, 296(2), E333-E342. https://doi.org/10.1152/ajpendo.90760.2008
Chen, C. Y., Tsai, Y. L., Kao, C. L., Lee, S. D., Wu, M. C., Mallikarjuna, K., Liao, Y. H., Ivy, J. L., & Kuo, C. H. (2010). Effect of mild intermittent hypoxia on glucose tolerance, muscle morphology and AMPK-PGC-1alpha signaling. The Chinese journal of physiology, 53(1), 62-71. https://doi.org/10.4077/cjp.2010.amk078
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
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
Godinho, R., Mega, C., Teixeira-de-Lemos, E., Carvalho, E., Teixeira, F., Fernandes, R., & Reis, F. (2015). The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A "Me Too" or "the Special One" Antidiabetic Class?. Journal of diabetes research, 2015, 806979. https://doi.org/10.1155/2015/806979
Bonnefond, A., Unnikrishnan, R., Doria, A., Vaxillaire, M., Kulkarni, R. N., Mohan, V., Trischitta, V., & Froguel, P. (2023). Monogenic diabetes. Nature reviews. Disease primers, 9(1), 12. https://doi.org/10.1038/s41572-023-00421-w
Sasaki, Y., Ihara, K., Matsuura, N., Kohno, H., Nagafuchi, S., Kuromaru, R., Kusuhara, K., Takeya, R., Hoey, T., Sumimoto, H., & Hara, T. (2004). Identification of a novel type 1 diabetes susceptibility gene, T-bet. Human genetics, 115(3), 177-184. https://doi.org/10.1007/s00439-004-1146-2
Osawa, H., Yamada, K., Tabara, Y., Ochi, M., Onuma, H., Nishida, W., Shimizu, I., Kawamoto, R., Fujii, Y., Miki, T., Ohashi, J., & Makino, H. (2008). The G/G genotype of a single nucleotide polymorphism at -1066 of c-Jun N-terminal kinase 1 gene (MAPK8) does not affect type 2 diabetes susceptibility despite the specific binding of AP2alpha. Clinical endocrinology, 69(1), 36-44. https://doi.org/10.1111/j.1365-2265.2007.03143.x
Yung, J. H. M., & Giacca, A. (2020). Role of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes. Cells, 9(3), 706. https://doi.org/10.3390/cells9030706
Stavarachi, M., Panduru, N. M., Serafinceanu, C., Moţa, E., Moţa, M., Cimponeriu, D., & Ion, D. A. (2011). Investigation of P213S SELL gene polymorphism in type 2 diabetes mellitus and related end stage renal disease. A case-control study. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 52(3 Suppl), 995-998.
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
