A small molecule 'exercise mimetic' may help control Type 2 diabetes and obesity

Researchers at the University of Southampton have developed a small molecule which they refer to as "Compound 14" that deceives cells into thinking they have run out of energy--spurring on glucose uptake and increasing metabolism.

Their findings were published in Chemistry and Biology and authored by Ali Tavassoli, a professor at the University of Southampton.

AMPK is a protein that acts as the cell's energy sensor, and the value of manipulating it has been long appreciated for metabolic disorders such as Type 2 diabetes and obesity.

The researchers activated this protein by blocking an enzyme called ATIC which increases a molecule known as ZMP in cells found upstream of AMPK and prompts AMPK into action. In doing so, they reported a reduction in fasting blood glucose levels, improved glucose tolerance and some weight loss in obese mice.

"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," says Tavassoli. "Our molecule, which activates AMPK by altering cellular metabolism, therefore holds much promise as a potential therapeutic agent."

There are no effective therapies for improving insulin sensitivity in patients with Type 2 diabetes. Compound 14 may address this issue and importantly works by reducing glucose levels and body weight only in subjects that are obese.

- here's the release

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