Published On: Wed, Jan 13th, 2016

Too much sugar? There’s an enzyme for that

Daily sugary drinks tied to increased visceral fat; Discovery of a glucose detoxification enzyme that provides novel therapeutics for obesity and diabetes

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Guilt-free sugary treats may be on the horizon. Scientists at the University of Montreal have discovered an enzyme that can stop the toxic effects of sugar in various organs of the body. This enzyme, named glycerol 3-phosphate phosphatase (G3PP), plays a central role in controlling glucose and fat utilization. Led by Drs Marc Prentki and Murthy Madiraju, The research team has demonstrated that G3PP is able to detoxify excess sugar from the cells, and their discovery should lead to the development of therapeutics for obesity and type 2 diabetes.

Mammalian cells use glucose and fatty acids as the main nutrients. Their utilization inside cells governs many physiological processes such as insulin secretion by beta cells, production of glucose in liver, storage of fat in adipose tissue and breakdown of nutrients for energy production. Derangement of these processes leads to obesity, type 2 diabetes and cardiovascular diseases. The beta cells sense changes in blood glucose levels and produce insulin according to body demand. Insulin is an important hormone for controlling glucose and fat utilization.

“By diverting glucose as glycerol, G3PP prevents excessive formation and storage of fat and it also lowers excessive production of glucose in liver, a major problem in diabetes, ” says Murthy Madiraju, a scientist at CRCHUM.

How significant are the findings? “It is extremely rare since the 1960s that a novel enzyme is discovered at the heart of metabolism of nutrients in all mammalian tissues, and likely this enzyme will be incorporated in biochemistry textbooks, ” Professor Prentki said. “We identified the enzyme while looking for mechanisms enabling beta cells to get rid of excess glucose as glycerol, adds Murthy Madiraju. This mechanism has also been found to be operating in liver cells, and this enzyme is present in all body tissues”.

The work offers a new therapeutic target for obesity, type 2 diabetes and metabolic syndrome. The research team is currently in the process of discovering “small molecule activators of G3PP” to treat cardiometabolic disorders. These drugs will be unique in their mode of action and first of their kind in this class of drugs. The treatment will first have to be confirmed in several animal models before drugs for human use can be developed.

 

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