Methyl ferulic acid ameliorates prolonged high insulin-induced insulin release and synthesis in pancreatic β-cells via the miR-378b–PI3K–AKT pathway

Abstract

Impaired insulin release and synthesis in β-cells is a major cause of the development of type 2 diabetes mellitus. Methyl ferulic acid (MFA) has potential antidiabetic properties, but its specific role in protecting against β-cell damage is not known. This research aimed to survey the effects of MFA on insulin release and synthesis in pancreatic β-cells induced by chronic high insulin, and to study the mechanisms underlying MFA. Our study found that miR-378b was upregulated in excessive insulin-induced pancreatic β-cells and in the pancreas of C57BL/6 mice, accompanied by reduced levels of insulin receptor (IR), p110α, p-AKT, and glucose-stimulated insulin release and synthesis. MFA treatment ameliorated high insulin-induced impairment of insulin release and synthesis by downregulating miR-378b, restoring IR and p110α levels, and attenuating apoptosis. In conclusion, our results show that MFA may serve as a valuable drug for the prevention and treatment of diabetes. The miR-378b–PI3K–AKT pathway may mediate the beneficial effects of MFA treatment.

Keywords

• Methyl ferulic acid
• miR-378b
• Insulin release and synthesis
• PI3K–AKT pathway