Enzyme that governs sugar metabolism may uncover treatments for obesity and diabetes
Scientists have uncovered a new enzyme that works to block the adverse effects of sugar on the body. Present in all mammals, the enzyme plays the role of disposing of the unwanted byproducts of heightened glucose levels. In discovering this key step in the metabolism of sugar, the scientists say they have uncovered a new therapeutic target for conditions like type 2 diabetes and obesity, and are now working to develop drugs that boosts its activity.
Dubbed glycerol 3-phosphate phosphatase (G3PP), the newly-discovered enzyme was happened upon by scientists at University of Montreal Hospital Research Centre (CRCHUM). The team was hunting for mechanisms that convert excess glucose in beta cells into glycerol, before diverting them outside the cell wall altogether. The hope is that if this process can be manipulated, then it may be possible to avoid the consequences of high glucose levels which can include obesity, diabetes and heart problems.
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"When glucose is abnormally elevated in the body, glucose-derived glycerol-3 phosphate reaches excessive levels in cells, and exaggerated glycerol 3 phosphate metabolism can damage various tissues," explains Marc Prentki, a principal investigator at the CRCHUM and professor at the University of Montreal. "We found that G3PP is able to breakdown a great proportion of this excess glycerol phosphate to glycerol and divert it outside the cell, thus protecting the insulin producing beta cells of pancreas and various organs from toxic effects of high glucose levels."
The scientists say that it has been rare in the last half a century to discover novel enzymes behind the metabolism of nutrients in mammal tissue, and that so significant are their findings that they may even prompt revisions to biochemistry textbooks.
They are now turning their attention to finding small molecules that can serve as activators of G3PP to treat sufferers of cardiometabolic disorders, those with heightened risk of diabetes, heart disease or stroke. These molecules would mark the beginnings of a new class of drugs, but the researchers note their effectiveness would first have to be established in animal models before being tested on humans.
The research was published in the journal Proceedings of the National Academy of Sciences.