Protein Tyrosine Phosphatase 1B is Impaired in Skeletal Muscle of Diabetic Psammomys Obesus

Protein tyrosine phosphatases (PTPases) have been suggestedto modulate the insulin receptor signal transduction pathways.Westudied PTPases in Psammomys obesus, an animal model of nutritionallyinduced insulin resistance. No changes in the proteinexpression level of src homology PTPase 2 (SHP-2) (muscle, liver)or leukocyte antigen receptor (LAR) (liver) were detected. In contrast,the expression level of PTPase 1B (PTP 1B) in the skeletalmuscle, but not in liver, was increased by 83% in the diabetic animals,compared with a diabetes-resistant line. However, PTP 1B–specific activity (activity/protein) significantly decreased (50% to56%) in skeletal muscle of diabetic animals, compared with boththe diabetes-resistant line and diabetes-prone animals. In addition,PTP 1B activity was inversely correlated to serum glucose level(r = –.434, P < .02). These findings suggest that PTP 1B, thoughoverexpressed, is not involved in the susceptibility to insulin resistancein Psammomys obesus and is secondarily attenuated byhyperglycemia or other factors in the diabetic milieu.