Early Alterations in the Expressions of MCTS and HIF‐1α in Experimental Diabetes Mellitus

Abstract

AimTo evaluate alterations due to the establishment of experimental diabetes mellitus (DM) alloxan‐induced in biochemical parameters and the expression of genes MCT1, MCT4, CD147 and HIF‐1α in different tissues and in the blood profile.MethodsWistar rats (120–180g) were conditioned at the FMABC bioterium in conditions of 12 hours light/dark, climate temperature (21 ± 2 °C) and ad libitum supply of water and food. Animals of the DM group were treated with Alloxan monohydrate (120 mg/kg) intraperitoneal (ip); the control group sham (NDS) received injections of sodium chloride 0,9% (ip). The glycemic values were measured weekly during the period of treatment through a commercial glycosimeter by puncturing of the caudal vein of the animal; animals with glycemia above ≥200 mg / dL were determined as diabetic. Evaluated the biochemical parameters: glycemia, blood creatinine and urea, and the expression of molecular biomarkers in the heart, brain, kidney and blood by the RT‐qPCR technique. Data was analyzed by GraphPad Prism® 6.0, statistical differences were observed by the Mann‐Whitney test and Student T test with an established significance level in 5% (descriptive value of p <0.05).ResultsThe biochemical parameters found were: glycemia (DM7 619.1 ± 140.7 * p <0.005, n = 10 vs NDS 192.5 ± 43.64, n = 4), blood creatinine (DM7 0.46 ± 0.05 * p <0.005, n = 10 vs NDS 0.40 ± 0.07, n = 4) and urea (DM7 96.7 ± 26.6 * p <0.005, n = 10 vs. NDS 46.5 ± 7.0, n = 4) these values follow the established standards for the diabetic profile in the present study. In the molecular analyzes an increase of CD147 in the brain was observed (DM7 26.72 ± 27.45, * p <0.005, n = 9 vs NDS 1,489 ± 1,648, n = 4). In the blood profile an enhancement in the expressions of all the genes studied in the animals with DM were found; MCT1 (DM7 3,739 ± 3,057 * p <0.005, n = 10 vs NDS 0.009745 ± 0.007489, n = 4); MCT4 (DM7 7.364 ± 7.3, * p <0.005 n = 10 vs NDS 0.06399 ± 0.04844, n = 3); CD147 (DM7 4,295 ± 4,424 * p <0.005, n = 10 vs NDS 0.2212 ± 0.01653, n = 4) and HIF‐1α (DM7 1,413 ± 1,087 * p <0.005, n = 10 vs NDS 0.003833 ± 0.003741, n = 4). A positive correlation between glucose and MCT1 in the blood profile (r = 0.8061, * p <0.05, n = 10) was also noted, Spearman test.ConclusionsPreliminary data demonstrate that even early DM promotes serious biochemical changes accompanied by modifications in the expression of genes involved with glycolytic metabolism and in the cellular hypoxia mechanism. Apparently, the brain is the first tissue affected by these changes.Support or Funding InformationCAPES and CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.