Bis(maltolato)oxovanadium(IV) inhibits the activity of PTP1B in Zucker rat skeletal muscle in vivo.
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.
Mohammad
Askar
A
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Wang
Jian
J
McNeill
John H
JH
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D014638:Vanadates / Q000494:pharmacology*
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D011753:Pyrones; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat