Deletion of protein tyrosine phosphatase 1B (PTP1B) prevents type 1 diabetes‐induced vascular dysfunction

Abstract

Impaired vascular function is a common feature in type I diabetic patients. PTP1B deletion prevents endothelial dysfunction and leptin infusion restores cardiovascular dysfunction induced by type I diabetes. We hypothesized that increasing leptin sensitivity via PTP1B deletion prevents vascular dysfunction in type I diabetic mice. Type I diabetes was induced with streptozotocin (STZ) in male and female Balb/C and PTP1B KO mice. Vascular function was studied after 24 days of STZ on aortic rings mounted on a wire myograph. Glycemia was significantly increased with STZ and further exaggerated by PTP1B deletion in male mice only (Balb/CMSTZ: 342±18 vs PTP1BMSTZ: 509±26 mg/dl, p<0.05). Endothelial function assessed via acetylcholine (ACh)‐mediated relaxation was reduced in both male and female Balb/C mice but preserved in PTP1B KO animals. While LNAME completely abolished ACh‐mediated relaxation in Balb/C mice, addition of indomethacin was required to abolish relaxation in PTP1B KO mice treated with STZ, suggesting dilatory cyclooxygenase derivatives involvement. Phenylephrine (PE)‐induced constriction was increased by STZ in male and female Balb/C, but preserved in PTP1B KO male mice only. Taken together these data indicate that PTP1B deletion protects against the harmful vascular effects of type I diabetes, independent of hyperglycemia and with more pronounced effects in male than female mice.