Scientists at the University of Southampton in England have developed a new molecule that that help treat type 2 diabetes and obesity.
"Compound 14" acts as an exercise mimic by interfering with the function of ATIC, a cellular enzyme involved in metabolism, leading to the build-up of a molecule called ZMP in cells. This makes cells think that they have run out of energy by activating the cell's central energy sensor, known as AMPK, thereby causing cells to try and increase their energy levels by increasing glucose uptake and metabolism.
Researchers found that activating AMPK with compound 14 reduced fasting blood glucose levels, improved glucose tolerance and, at the same time, promoted 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," researcher Ali Tavassoli said in a statement. "Our molecule, which activates AMPK by altering cellular metabolism, therefore holds much promise as a potential therapeutic agent."
For the study, the molecule was given to two groups of mice who were fed either a normal diet or a high-fat diet making them obese and impairing their glucose tolerance (one of the clinical signs of pre-diabetes). When mice with a normal diet were treated with compound 14, their blood glucose levels and weight remained normal. However, in obese mice on the high-fat diet a single dose of compound 14 resulted in lowering their elevated blood glucose close to near normal levels. Furthermore, a daily dose of compound 14 administered for seven days to the obese mice resulted in improved glucose tolerance and a five percent loss in body weight. Compound 14 did not affect the weight of those mice on the normal diet.
"Current treatments for type 2 diabetes centers on elevating circulating insulin levels or improving the insulin sensitivity of an individual. 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," Dr. Felino Cagampang, co-author of the study, said in a statement.
Researchers will develop the molecule further to examine the effect of long-term treatment and its mode of action in improving glucose tolerance and in reducing body weight.
The study is detailed in the journal Chemistry & Biology.
