Alteration in Gene Expression of STAT4 and PIAS2 in Individuals with Type 2 Diabetes Mellitus Treated with the Dipeptidyl Peptidase 4 InhibitorSina Nabiyi, Firozeh Sajedi, Alireza Zamani, Mahdi Behzad
Objective: Impairment of immune cell signaling molecules is involved in diseases pathogenesis. The evaluation of signal transducer and activator of transcription (STAT) 4 and protein inhibitor of activated STAT (PIAS) 2 as well as immunoregulatory role of the dipeptidyl peptidase-4 inhibitor, sitagliptin were investigated in type 2 diabetes mellitus (T2DM).
Materials and Methods: Peripheral blood mononuclear cells were purified from three study groups including healthy controls, T2DM patients with 6 months of sitagliptin treatment, and T2DM patients without sitagliptin. Expressions of STAT4 and PIAS2 were assessed with real-time polymerase chain reaction (qPCR).
Results: The expression of STAT4 in patients without sitagliptin was higher than the healthy controls (p=0.001). Its expression was down-regulated in the sitagliptin treated patient group compared to those without sitagliptin (p=0.005). PIAS2 expression in patients without sitagliptin was lower than the healthy controls (p=0.009). PIAS2 was elevated in the sitagliptin treated group versus patients without sitagliptin (p=0.003). A negative correlation between STAT4 and PIAS2 was found in individuals without sitagliptin (p=0.01). In patients without sitagliptin, fasting plasma glucose was positively and negatively correlated with STAT4 and PIAS2, respectively (p=0.004 and p=0.001).
Conclusion: Aberrant expression of STAT4 and reduced expression of PIAS2 were found in the T2DM patients. Sitagliptin may regulate the cell signaling pathways by elevating PIAS2 and reducing STAT4.