METFORMIN AS A TRANSCRIPTIONAL REGULATOR OF INSULIN MEDIATORS IN A PRENATAL HYPERANDROGENIZED RAT MODEL

MARIA FLORENCIA HEBER; GISELLE ADRIANA ABRUZZESE; ALICIA BEATRIZ MOTTA; SILVANA ROCIO FERREIRA

Mar del Plata

Congreso; Reunión Anual LXI SAIC, LXIV SAI, XLVIII SAFE Mar del Plata, Buenos Aires, Argentina, noviembre 2016; 2016

SAIC, SAI, SAFE

Around 70% of women with Polycystic ovary syndrome (PCOS) develop insulin resistance (InR), a state that affects tissues differentially. Insulin responsiveness of target tissues in women with PCOS has been studied at a functional level, but little is known about transcriptional regulation. Insulin sensitizer drugs such as metformin (Met) improve InR as well as reproductive abnormalities in PCOS. Here, we tested the effects of androgen excess on the gene expression of key molecules of the insulin signaling pathway and the effects of Met on the deregulations found. A prenatal hyperandrogenization (PH) model was used. Control (C) and PH rats were euthanized at 90 days of age (adulthood, N=80). From day 70 to 90, 20 rats of each group were treated orally daily with 50 mg/kg of Met (PHM). We evaluated serum insulin and glucose levels and the HOMA-IR index. Gene expression of the insulin receptor (IR), insulin substrate 1 and 2 (IRS-1, IRS-2) and glucose transporters (GLUT2 and GLUT4) was measured by qPCR in hepatic and ovarian tissue. Serum insulin and glucose levels and the HOMA-IR index were higher in PH group vs C, and Met restored the levels to those of the C group (p