Anti-diabetic effect of hydroxybenzoic acid derivatives in free fatty acid-induced HepG2 cells via miR-1271/IRS1/PI3K/AKT/FOXO1 pathway

Type 2 diabetes is characterized by insulin resistance (IR) and increased hepatic glucose production. MicroRNAs (miRs) are considered regulators of glucose metabolism. This study evaluated anti-diabetic activity of hydroxybenzoic acid derivatives and determined the involvement of miR-1271. Among the hydroxybenzoic acid derivatives, gallic acid (GA) showed the best anti-diabetic activity. GA improved free fatty acid (FFA)-induced hepatic IR, increased glucose consumption, and decreased reactive oxygen species. GA inhibited the upregulation of miR-1271 induced by FFA and upregulated its targets such as p-IRS, p-PI3K, p-AKT, and p-FOXO1, accompanied by the regulation of glucose metabolism genes. The involvement of miR-1271 in the protective effect of GA against IR was further confirmed in the presence of miR-1271 mimic or miR-1271 inhibitor. Our results suggest that GA attenuates IR via the miR-1271/IRS/PI3K/AKT/FOXO1 pathway and thus might be considered for the management of IR.