Determination and analysis of gene expression involved in glucose metabolism under the conditions of the development of experimental diabetes of dexamethasone type (type 2 diabetes)

Authors

DOI:

https://doi.org/10.14739/2409-2932.2024.3.313140

Keywords:

pancreas, diabetes, genes, insulin, insulin resistance, laboratory diagnosis

Abstract

Type 2 diabetes is one of the most common and serious chronic diseases today, which has become a global health care problem. Type 2 diabetes accounts for about 90–95 % of all cases of diabetes and significantly affects patients’ quality life due to the development of numerous complications, such as cardiovascular diseases, chronic renal failure, retinopathy, neuropathy. Modern research in the field of diabetology pays considerable attention to the understanding of the genetic mechanisms of the pathogenesis of type 2 diabetes, which makes it possible to develop new approaches to its diagnosis and treatment. Individualization of laboratory diagnostics and treatment, which considers the genetic, metabolic and clinical characteristics of each patient, is a key direction in improving the effectiveness of the treatment of type 2 diabetes. Type 2 diabetes is a complex polygenic disease, that develops under the influence of both genetic and external factors, which requires an integrated approach to its diagnosis, treatment and prevention. Taking into account the constant increase in the prevalence of this disease, the relevance of scientific research in this area is beyond doubt. The development of new pharmacological agents, improvement of laboratory diagnostic strategies and individualization of treatment are key directions for overcoming the problem of type 2 diabetes and improving the quality of life of patients.

The aim of the work: identification and analysis of genes panel, involved in glucose metabolism under the conditions of the development of experimental type 2 diabetes.

Materials and methods. Analysis of the gene expression, involved in glucose metabolism was performed using the real-time reverse transcription polymerase chain reaction method CFX-96 Touch™ (Bio-Rad, USA) using the RT2Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany).

Results. Based on the results of the PCR study, the activity of the studied genes involved in glucose metabolism can be divided as follows: G6pc, Gpd1 – genes with high expression compared to the control group of animals; Ace, Acly, Foxg1, Foxp3, Gcgr, Gck, Gsk3b, Hmox1, Pygl, Snap23, Snap25 – genes with low expression compared to the control group of animals; Cebpa, Dpp4, Sell – genes in which no changes were detected in the samples in relation to the control group of animals; Ccr2, Fbp1, Gcg – genes, whose expression was not detected.

Conclusions. The development of dexamethasone type 2 diabetes significantly (where ∆∆Ct <30) increases the expression of Gpd1 genes by 8 times and G6pc by 2 times compared to the control group of animals. During the development of type 2 dexamethasone diabetes, significantly (where ∆∆Ct <30) the Gsk3b and Hmox1 genes had a 17-fold low expression; Pygl at 11; Foxg1 in 7; Gck in 6; Ace and Foxp3 in 4; Acly in 3; Gcgr, Snap23, Snap25 in 2 times compared to the control group of animals. The expression of Ccr2, Fbp1, Gcg genes during the development of type 2 dexamethasone diabetes was not detected.

Author Biographies

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

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

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

Postgraduate Student of the Department of Clinical Laboratory Diagnostics

References

Magliano DJ, Boyko EJ. IDF diabetes atlas [Internet]. 10th edition. Brussels: International Diabetes Federation; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK581934/

American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S144-74. doi: https://doi.org/10.2337/dc22-S010

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. doi: https://doi.org/10.1016/j.diabres.2019.107843

Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006;23(5):469-80. doi: https://doi.org/10.1111/j.1464-5491.2006.01858.x

Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001;345(11):790-7. doi: https://doi.org/10.1056/NEJMoa010492

Mahajan A, Taliun D, Thurner M, Robertson NR, Torres JM, Rayner NW, et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet. 2018;50(11):1505-13. doi: https://doi.org/10.1038/s41588-018-0241-6

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

Nordlie RC, Foster JD, Lange AJ. Regulation of glucose production by the liver. Annu Rev Nutr. 1999;19:379-406. doi: https://doi.org/10.1146/annurev.nutr.19.1.379

Huang Y, Hu K, Lin S, Lin X. Glycerol-3-phosphate acyltransferases and metabolic syndrome: recent advances and future perspectives. Expert Rev Mol Med. 2022;24:e30. doi: https://doi.org/10.1017/erm.2022.23

Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012;148(5):852-71. doi: https://doi.org/10.1016/j.cell.2012.02.017

Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A, et al. Glucose-6-phosphatase deficiency. Orphanet J Rare Dis. 2011;6:27. doi: https://doi.org/10.1186/1750-1172-6-27

Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840-6. doi: https://doi.org/10.1038/nature05482

Barthel A, Schmoll D. Novel concepts in insulin regulation of hepatic gluconeogenesis. Am J Physiol Endocrinol Metab. 2003;285(4):E685-92. doi: https://doi.org/10.1152/ajpendo.00253.2003

Rhoads AR, Karkera JD, Detera-Wadleigh SD. Radiation hybrid mapping of genes in the lithium-sensitive wnt signaling pathway. Mol Psychiatry. 1999;4(5):437-42. doi: https://doi.org/10.1038/sj.mp.4000538

Abraham NG, Kappas A. Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev. 2008;60(1):79-127. doi: https://doi.org/10.1124/pr.107.07104

Hers HG. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167-89. doi: https://doi.org/10.1146/annurev.bi.45.070176.001123

Kim CH. FOXP3 and its role in the immune system. Adv Exp Med Biol. 2009;665:17-29. doi: https://doi.org/10.1007/978-1-4419-1599-3_2

Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab. 2022;66:101633. doi: https://doi.org/10.1016/j.molmet.2022.101633

Matschinsky FM. Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics. Diabetes. 2002;51(Suppl 3):S394-S404. doi: https://doi.org/10.2337/diabetes.51.2007.s394

Coleman CI, Weeda ER, Kharat A, Bookhart B, Baker WL. Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal and mortality outcomes in people with Type 2 diabetes and proteinuria. Diabet Med. 2020;37(1):44-52. doi: https://doi.org/10.1111/dme.14107

Zhao S, Torres A, Henry RA, Trefely S, Wallace M, Lee JV, et al. ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch. Cell Rep. 2016;17(4):1037-52. doi: https://doi.org/10.1016/j.celrep.2016.09.069

Li M, Sun C, Bu X, Que Y, Zhang L, Zhang Y, et al. ISL1 promoted tumorigenesis and EMT via Aurora kinase A-induced activation of PI3K/AKT signaling pathway in neuroblastoma. Cell Death Dis. 2021;12(6):620. doi: https://doi.org/10.1038/s41419-021-03894-3

Liang T, Qin T, Kang F, Kang Y, Xie L, Zhu D, et al. SNAP23 depletion enables more SNAP25/calcium channel excitosome formation to increase insulin exocytosis in type 2 diabetes. JCI Insight. 2020;5(3):e129694. doi: https://doi.org/10.1172/jci.insight.129694

Sadoul K, Lang J, Montecucco C, Weller U, Regazzi R, Catsicas S, et al. SNAP-25 is expressed in islets of Langerhans and is involved in insulin release. J Cell Biol. 1995 Mar;128(6):1019-28. doi: https://doi.org/10.1083/jcb.128.6.1019

Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 2006;116(1):115-24. doi: https://doi.org/10.1172/JCI24335

Pack M, Gulde TN, Völcker MV, Boewe AS, Wrublewsky S, Ampofo E, et al. Protein Kinase CK2 Contributes to Glucose Homeostasis by Targeting Fructose-1,6-Bisphosphatase 1. Int J Mol Sci. 2022;24(1):428. doi: https://doi.org/10.3390/ijms24010428

Additional Files

Published

2024-11-08

How to Cite

1.
Ivanenko TV, Vynokurova AV. Determination and analysis of gene expression involved in glucose metabolism under the conditions of the development of experimental diabetes of dexamethasone type (type 2 diabetes). Current issues in pharmacy and medicine: science and practice [Internet]. 2024Nov.8 [cited 2024Dec.5];17(3):262-6. Available from: http://pharmed.zsmu.edu.ua/article/view/313140