Protein tyrosine phosphatase 1B is impaired in skeletal muscle of diabetic Psammomys obesus.

Yukio Ikeda,Eleazar Shafrir,Ehud Ziv,Luitgard Mosthaf-Seedorf

doi:10.1080/15604280214275

Abstract

Protein tyrosine phosphatases (PTPases) have been suggested to modulate the insulin receptor signal transduction pathways.We studied PTPases in Psammomys obesus, an animal model of nutritionally induced insulin resistance. No changes in the protein expression 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 skeletal muscle, 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% to 56%) in skeletal muscle of diabetic animals, compared with both the 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, though overexpressed, is not involved in the susceptibility to insulin resistance in Psammomys obesus and is secondarily attenuated by hyperglycemia or other factors in the diabetic milieu.

Highlights

The desert gerbil Psammomys obesus is an animal model of insulin resistance and nutritionally induced diabetes
Some studies have reported the influence of hyperinsulinemia or hyperglycemia on PTPase 1B (PTP 1B) content or Protein tyrosine phosphatases (PTPases) activity in vitro [27, 28]
Ahmad and Goldstein [29] demonstrated that the particulate PTPase activity toward both myelin basic protein and lysozyme was increased in hindlimb skeletal muscle of insulinresistant obese and diabetic (ZDF/Drt-fa/fa) Zucker rats

Summary

Introduction

The desert gerbil Psammomys obesus ( known as sand rat) is an animal model of insulin resistance and nutritionally induced diabetes. The IR-TK activity is regulated through autophosphorylation of tyrosine residues [6, 7], dephosphorylation by protein tyrosine phosphatases (PTPases) [8, 9], and inhibitory serine/threonine phosphorylation [10, 11]. The reason for the attenuation of insulin signaling in Psammomys could be enhanced PTPase activity and/or increased activity of serine/threonine kinases. The latter possibility was confirmed in a recent study in which we found that protein kinase Cε (PKCε) and several other PKC. The aim of our study was to clarify whether alterations in the protein expression level or activity of PTPases could contribute to the development or progression of insulin resistance through dephosphorylation of IR-TK and other components of the signaling pathway. The cDNA for the type A IR [20] was cloned into a cytomegalovirus promotor-enhancer– driven expression vector

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