Stafforshire University, UK
26 Aug 2012
28 Feb 2013
1 May 2013
glucose-6-phosphatase, vanadyl sulphate, vanadyl acetylacetonate, type 2 diabetes, inhibition, therapeutics
Type 2 diabetes is a major chronic health condition in which hyperglycaemia has significant impact on morbidity and mortality, and its ever-increasing incidence has made the production of therapeutic agents for type 2 diabetes more necessary. Vanadium compounds are known to control hyperglycaemia but the exact focus of where they work is a matter of debate. A proposed mechanism of action is that it inhibits glucose-6-phosphatase, a key enzyme in the development of insulin resistance and thus type 2 diabetes. This paper looks at the inhibitory effects of vanadium salts on glucose-6-phosphatase and also studies the mechanism of inhibition, the hypothesis being that the two vanadium compounds, vanadyl sulphate (VOSO4) and vanadyl acetylacetonate (Vace) will inhibit glucose-6-phosphatase. This was achieved by using a proof of principle study by extracting glucose-6-phosphatase from bovine liver microsomes using differential centrifugation, and then the enzyme was assayed in the presence and absence of vanadium compounds. The study found that vanadyl compounds inhibit glucose-6-phosphatase, as mean specific enzyme activity was calculated which showed that VOSO4 at a concentration of 48 µM inhibited glucose-6-phosphatase activity by 36.9% (P < 0.0003) and Vace at a concentration of 200 µM inhibited glucosse-6-phosphatase activity by 50% (P < 0.0001) similar to findings in the previous research. However, this study also found using Lineweaver–Burk plot analysis that VOSO4 is a competitive inhibitor of glucose-6-phophatase and Vace is a mixed: non-competitive and uncompetitive inhibitors of glucose-6-phosphatase. The mechanism of inhibitory action of these vanadyl compounds had not been reported previously. The difference in the concentration of inhibitor required may be due to the type of inhibition. This supports the hypothesis to some extent as the results were found to be statistically significant; however, further data will be required to clarify these findings.