Updated on 25 November 2013
The breakthrough in pinning down how the drug functions began with the researchers making genetic mutations to the genes of two enzymes, ACC1 and ACC2, in mice, so they could no longer be controlled. What happened next surprised the researchers: the mice didn't get fat as expected, but associate professor Dr Gregory Steinberg at McMaster University noticed that the mice had fatty livers and a pre-diabetic condition. Then the researchers put the mice on a high fat diet and they became fat, while metformin did not lower the blood sugar levels of the mutant mice.
The findings are expected to now help researchers better directly target the condition that affects over 100 million people around the world, according to published reports. It is also believed that with the mystery of metformin solved, the application of the drug could go beyond just diabetes and potentially be used to treat other medical conditions.
"AB SCIEX mass spectrometry solutions help researchers explore big questions and conduct breakthrough studies, such as this remarkable type 2 diabetes study," said Mr Rainer Blair, president of AB Sciex. "In order to understand disease at the molecular level, researchers need the sensitive detection and reproducible quantitation provided by AB SCIEX tools. We enable the research community to solve biological mysteries and rethink the possibilities to transform health."
For the research conducted by the Australian and Canadian researchers, the analysis at the molecular level was optimized on AB S ciex instrumentation, including the AB Sciex TripleTOF 5600 and the AB Sciex QTRAP 5500 system. The TripleTOF system, with its high-speed, high-quality MS/MS capabilities, was used for the discovery of key proteins and phosphopeptides. The QTRAP system, with its high sensitivity multiple reaction monitoring (MRM) capabilities, was used for quantitation of metabolites, including nucleotides and malonyl-CoA.