Author(s): JS Joseph and OF Fagbohum
Source: Comparative Clinical Pathology https://doi.org/10.1007/s00580-022-03318-4
Abstract: More than 90% of diabetes cases are type 2 diabetes characterized by persistent increase in glucose (hyperglycemia), lipid, and protein metabolic disorders that may induce insulin resistance. Individuals who suffer from type 2 diabetes are partly characterized by down-regulation of glucose transport and mitochondrial lipid oxidizing genes. Nuclear respiratory factor, (NRF)-1, is a mitochondrial transcriptional factor shown to be involved in glucose transport and acts as potential therapeutic modality in the management of T2DM. In this study, we accessed NRF-1 and its target gene expression crucial in glucose transport and lipid oxidation during exercise. Five- to 6-week-old male Wistar rats were exercised to identify the time-point for an optimum increase in the levels of NRF-1 and target genes. Gastrocnemius muscles were harvested after 0, 2, 4, 6, 8, 10, 12, and 15 h post-exercise and non-exercise rats. Primers were used to amplify the region of the genes; Nrf-1, glut 4, carnitine palmitoyltransferase, peroxisome proliferator-activated receptor gamma co-activator 1, mef2a, and acetyl-CoA carboxylase-1. Relative mRNA expression was normalized to the Actin reference gene. Cpt-1, Nrf-1, mef2a, glut4, cpt2, and Pgc-1 showed 2.5, 8, 1.2, 4.1, 4.6, 3.5-folds increase respectively after 8 h post-exercise compared with control, whereas Acc-1 showed a 3.1-fold decrease in gene expression ratio after 6 h post-exercise. Nrf-1 binding to cpt-1 and mef2a increased with 3 and 3.5-folds, respectively. Nrf-1 was increased by exercise with its binding to target genes which has huge implications in ameliorating type 2 diabetes and insulin resistance.
Keywords: Type 2 diabetes; NRF; Exercise; Glut4; Lipid oxidation; Glucose transport