Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki (Jul 2023)
Determination of molecular mechanisms of development and course of experimental diabetes mellitus in Wistar rats
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.
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