miRNA array and oxi-proteome analyses reveal posttranscriptional actions of T3 on diabetic rats’ liver that could improve glycemia control

Diabetes mellitus (DM) has a multifactorial etiology including diverse molecular alterations comprising transcriptional and posttranslational mechanisms. Studies from our group have shown that DM-induced rats present primary hypothyroidism and that 3,5,3´ Triiothyronine (T3) treatment improves their glycemia control by reducing inflammatory cytokines expression in insulin-responsive tissues, and hepatic glucose production. Taking into account the complexity of DM etiology and treatment and the different mechanisms by which T3 induces its effects, this study aimed to evaluate the involvement of posttranscriptional mechanisms in the alterations of DM rats’ liver subjected to T3 treatment using miRNA PCR array and oxi-proteome analyses. DM was induced in 8-week-old Wistar rats by alloxan injection, and a subset of DM rats was treated with T3 (0.15 μg/kg BW) for 28 days. miRNA PCR array was used to analyze the expression of a set of 84 miRNAs implicated in DM, while oxidative damage of liver proteins, represented by protein carbonylation, was determined by 2D-DIGE method followed by mass spectrometry. This study identified by PCR array and validated by qPCR 10 de-regulated miRNAs (miR-21-5p, miR-29 a-c; miR-34a-5p; miR-96-5p; miR-122; miR-183-5p; miR-184 and miR-320) involved in insulin, glucose and inflammatory cellular response, additionally a decrease in oxidative damage of GCC2, CTH, CPS1, DMGDH, RGN and HP proteins related to glucose metabolism control, hormonal cellular response, and apoptosis processes in T3-treated vs untreated DM rats (P<0,05). The results indicate that T3 acts by different posttranscriptional mechanisms, favoring the improvement of glucose homeostasis of DM rats.