The
insulin signalling pathway consists of a series of phosphorylation and dephosphorylation steps inside the target cell.
Phosphotyrosine phosphatase 1B (PTP1B) dephosphorylates
phosphotyrosine (pTyr) residues present on the
insulin receptor (IR). In this study we examined the effect of
bis(maltolato)oxovanadium(IV) (BMOV) on PTP1B and its possible role in the amelioration of
insulin resistance. Fourteen to sixteen week old fatty Zucker rats (F), an animal model of
insulin resistance, were treated with BMOV in
drinking water for 3 weeks (FT) along with age matched lean littermate controls. The fatty rats responded to
vanadium with a significant decrease in plasma
insulin, (F = 5.1+/-0.8 FT = 3.3+/-0.7 ng/ml). During
insulin resistance the activity of PTP1B has been shown to increase, thus diminishing
insulin signalling in the target tissues. Hence, PTP1B is an important target for anti-diabetic
drug research. In our investigation we found that the PTP1B activity was increased to 200% in the skeletal muscle of untreated Zucker fatty rats compared to lean littermates. Three weeks of BMOV treatment reduced the activity of PTP1B by 25% in fatty treated rats, in vivo, compared to untreated fatty rats. There was no significant change in the activity of PTP1B in the lean treated rats. There was also no difference in the gene expression of PTP1B in the skeletal muscle of different groups of rats.
Vanadium compounds also inhibited PTP1B in vitro. These results indicate that PTP1B may be a potential target for the action of BMOV at least in the Zucker fatty rat model.