Analysis of molecular mechanisms of the development of experimental diabetes in Wistar rats under conditions of intermittent hypoxia

Abstract

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.

Keywords

• wistar rats
• diabetes
• pancreas
• hypoxia