Molecular mechanisms of regulation and damage of β-cells in the development of experimental dexamethasone-induced diabetes

T. V. Ivanenko; A. V. Vynokurova

doi:10.14739/2310-1237.2025.3.339549

Authors

T. V. Ivanenko Zaporizhzhia State Medical and Pharmaceutical University, Ukraine https://orcid.org/0000-0001-6617-5178
A. V. Vynokurova Zaporizhzhia State Medical and Pharmaceutical University, Ukraine https://orcid.org/0009-0008-5380-6071

DOI:

https://doi.org/10.14739/2310-1237.2025.3.339549

Keywords:

pancreas, diabetes mellitus, genes, insulin, insulin resistance, differentiation, β-cells, apoptosis, proliferation, autoimmune destruction, laboratory diagnostics

Abstract

According to the World Health Organization (WHO), diabetes mellitus remains one of the most prevalent and rapidly increasing non-communicable chronic diseases worldwide. Over the past few decades, there has been a consistent trend towards an increase in the number of patients in developed, as well as low- and middle-income countries. This trend is driven by a complex set of factors, including urbanization, sedentary lifestyles, poor nutrition, overweight and obesity, population aging, as well as comorbid pathology.

The aim of this study was to identify and analyse the expression of genes involved in the morphological and secretory regulation of β-cells and their alterations in response to damage under conditions of the development of experimental dexamethasone-induced diabetes.

Materials and methods. The analysis of gene expression involved in the morphological and secretory regulation of β-cells, as well as changes associated with their damage, was performed using real-time reverse transcription polymerase chain reaction on a CFX-96 Touch™ amplifier (Bio-Rad, USA) with the RT²Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany).

Results. Based on the PCR analysis, the activity of the investigated genes involved in the morphological and secretory regulation of β-cells can be categorized as follows: Parp1 – a gene exhibiting increased expression compared to the control group of animals; Enpp1, Ide, Trib3, Ucp2, Ccl5, Cd28, Icam1, Il12b, Tgfb1, Tnfrsf1a – genes demonstrating decreased expression compared to the control group of animals; Ceacam1, Dusp4, Retn, Ctla4, Ifng, Ikbkb, Il10, Il4r, Il6, Igfbp5, Tnf – genes in which no significant changes were detected in the samples relative to the control group of animals; Adra1a, Agt, Foxc2, Slc2a4, Srebf1, Tnfrsf1b – genes whose expression was not detected.

Conclusions. The development of dexamethasone-induced diabetes significantly increased expression (ΔΔCt < 30) of the Parp1 gene by 3.06-fold compared with the control group of animals. Under dexamethasone-induced diabetes, significantly decreased expression (ΔΔCt < 30), relative to the control group, was observed for the following genes: Enpp1 (12.55-fold), Ide (3.31-fold), Trib3 (7.74-fold), and Ucp2 (9.76-fold), which are involved in the mechanisms of insulin secretion regulation, Ccl5 (2.27-fold), Cd28 (23.98-fold), Icam1 (4.54-fold), Il12b (4.38-fold), and Tgfb1 (3.76-fold), which are associated with autoimmune destruction of β-cells; and Tnfrsf1a (130.97-fold), which is implicated in survival and apoptosis mechanisms. The expression of Adra1a, Agt, Foxc2, Slc2a4, Srebf1, and Tnfrsf1b was not detected under conditions of dexamethasone-induced diabetes.

Author Biographies

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

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

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

Postgraduate of the Department of Clinical Laboratory Diagnostics

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