Insulin signaling and glucose homeostasis in mice lacking protein tyrosine phosphatase α

Studies in cultured cells have implicated protein tyrosine phosphatase α (PTPα) as a potential regulator of insulin signaling. The physiological role of PTPα in insulin action was investigated using gene-targeted mice deficient in PTPα. PTPα-null animals had normal body weights and circulating levels of glucose and insulin in random fed and fasted states. In glucose and insulin tolerance tests, their efficiency of blood glucose clearance was comparable to wild-type mice. Kinetics and extents of insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation were similar in wild-type and PTPα−/− liver, muscle, and adipose tissue. However, the association of IRS-1 and PI 3-K was altered in PTPα−/− liver, with increased insulin-independent and reduced insulin-stimulated association compared to wild-type samples. This did not affect activation of the downstream signaling effector Akt. Our data indicate that PTPα is not a negative regulator of insulin signaling and does not perform an essential role in mediating the physiological action of insulin.