A novel function for endothelial protease-activated receptors in modulating insulin receptor activity with implications for diabetes.

ABSTRACT: Thrombin, a serine protease with increased activity in diabetics, signals through protease-activated receptors 1 and 4 (PAR1/PAR4) on endothelial cells (ECs). While studying the roles of endothelial PAR1/4 in diabetic pathology, we found that mice with inducible deletion of both receptors on ECs (Par1/4 ^iECko ) displayed increased insulin sensitivity and were protected against streptozotocin (STZ)-induced diabetes. Concordantly, we found that cultured primary ECs with PAR1/4 deficiency had increased basal activity/phosphorylation of the insulin receptor (IR) and insulin transcytosis. This elevated IR activity correlated with reduced activity of protein tyrosine phosphatase 1B (PTP1B), which is a negative regulator of IR activity. Lastly, Par1/4 ^iECko

SUBMITTER: Rajala R 

PROVIDER: S-EPMC11974755 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature