Linoleic acid exerts antidiabetic effects by inhibiting protein tyrosine phosphatases associated with insulin resistance

The regulation of protein tyrosine phosphorylation by protein tyrosine kinases and protein tyrosine phosphatases (PTPs) is involved in intracellular signaling pathways, such as cell proliferation, differentiation, migration, and metabolism. As inhibitors of certain PTPs associated with insulin resistance have been shown to improve insulin sensitivity, the use of inhibitors against PTPN1, PTPN9 or PTPN11 is considered an effective strategy for treating type 2 diabetes. Herein, for the first time, we revealed that linoleic acid (LA) inhibited the catalytic activity of PTPN1, PTPN9 and PTPN11 in vitro, indicating that LA targeted PTPN1, PTPN9, and PTPN11. Additionally, 40 μM LA treatment enhanced glucose uptake through activation of the AMPK and Akt signaling pathways. Taken together, these findings indicate that LA, a multi-targeting inhibitor of PTPN1, PTPN9, and PTPN11, may exert antidiabetic effects to prevent type 2 diabetes.