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Researchers develop molecule that mimics effects of exercise, could treat obesity and type 2 diabetes

Researchers from the University of Southampton have developed a new compound that mimics the benefits of exercise in people with type 2 diabetes.
The molecule, which is known as “compound 14,” blocks an enzyme called ATIC, which has an important function in metabolism.
By blocking ATIC, compound 14 causes a molecule called ZMP to build up. ZMP makes the central energy sensors of cells (these are known as AMPK) think that energy are levels are low. In response, the cells increase their uptake of glucose, thereby lowering blood sugar levels.
This is similar to the effects of exercise, which also triggers an increased glucose uptake by the cells.
The researchers conducted the study on two groups of mice: the first was fed a normal diet; the second was fed a diet designed to make them obese and glucose intolerant. Both groups were given compound 14.
The first group remained at a normal weight, and kept their normal blood glucose levels. But the second group – the group put on a bad diet – lost five per cent of their body weight, lowered their blood glucose levels, and generally improved their glucose tolerance. The normal-diet group of mice did not lose weight when given compound 14, but they didn’t need to.
Compound 14 could lead to new and improved treatments for obesity – by triggering weight loss – and type 2 diabetes – by lowering blood glucose levels. Compound 14 could particularly help the significant portion of people with type 2 diabetes whose blood glucose levels may not benefit from exercise.
“Current treatments for type 2 diabetes centre on elevating circulating insulin levels or improving the insulin sensitivity of an individual,” said Dr. Felino Cagampang, associate professor in integrative physiology at the University of Southampton.
“The issue is that established drugs do not successfully enable patients with type 2 diabetes to achieve glycemic control and some can even result in weight gain, a leading factor driving the diabetes epidemic.
“In contrast, this new molecule seems to reduce glucose levels and at the same time decrease body weight, but only if the subject is obese.”
Although highly promising, the research remains at a preliminary stage. This study was only conducted on mice, and the immune systems of humans may not work in the same way.
But the researchers are hopeful about the potential of their findings. Next, they hope to monitor compound 14’s long-term benefits regarding weight loss and blood glucose levels. If further trials are successful, compound 14 could form the basis of new treatments for obesity and high blood glucose levels.
Lead author Ali Tavassoli, professor of chemical biology at the University of Southampto, added:
“There is a lot of evidence from previous studies that if you could selectively activate AMPK with a small molecule, it could have potential benefits in the treatment of several diseases, including type 2 diabetes, by acting as an exercise mimetic and increasing the uptake and usage of glucose and oxygen by cells.
“Our molecule, which activates AMPK by altering cellular metabolism, therefore holds much promise as a potential therapeutic agent.”
The results were published in Chemistry and Biology.

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