Effects of folic acid on the IRS-PI3K-AKT pathway in an in vitro insulin resistance model.

INTRODUCTION: Insulin resistance (IR) occurs when insulin is ineffective in activating the IRS-PI3K-AKT pathway. Folic acid is used to prevent neural tube defects during pregnancy but the effects of folic acid supplementation on IR in maternal diabetes remain unclear. This study aimed to evaluate the effects of folic acid on an in vitro IR model. Therefore, we investigated the impact of folic acid on the IRS-PI3K-AKT pathway in relation to IR. METHODS: In vitro low and high dose IR models were carried out in human umbilical vein endothelial cells (HUVECs). Folic acid was applied at three different doses. Cell viability was measured using WST-1 analysis. Phospho-IRS-1, phospho-PI3K, and phospho-AKT levels were assessed via both immunocytochemistry and ELISA. RESULTS: Twenty-four hours after folic acid treatment, cell viability in the high dose-IR was higher than in the control group (p < 0.05). Forty-eight hours after folic acid treatment, cell viability was significantly lower in all three dose groups compared to the control group (p < 0.05). In both IR groups, the activity of the phospho-PI3K and phospho-AKT proteins was lower than in the control group. Following folic acid treatment, the activity of these proteins was higher than in both IR groups (p < 0.05). However, the reduced activity of the phospho-IRS-1 protein remained unchanged. CONCLUSIONS: The present study suggest that folic acid may protect HUVECs under IR conditions relevant to maternal diabetes, possibly via the IRS-PI3K-AKT pathway. Our results may provide new approaches regarding the possible protective effect of folic acid in diabetic vasculopathy.