University of Cincinnati (UC) scientists have identified a possible new target for treating obesity and diabetes.
The new target, a molecule called hVps34, is activated by amino acids (nutrients) entering the cell. This molecule triggers the activation of an enzyme, S6 Kinase 1 (S6K1), whose function UC researchers linked last year to obesity and insulin resistance.
"Insulin and amino acids both play a critical role in growth and development," said lead author George Thomas, PhD, interim director of UC's Genome Research Institute and Department of Genome Science. "Both are responsible for 'driving' cell growth. Now we have found that they actually work through independent pathways to trigger a molecule that turns on S6K1.
"Since we know S6K1 is linked to obesity and insulin resistance," he added, "learning that it can actually be turned on by more than one pathway is important, because it represents a potential target to regulate obesity."
The findings appear in the Sept. 19, 2005, online edition of Proceedings of the National Academies of Sciences (PNAS).
In 2004, Dr. Thomas led research that identified S6K1's function. Normally turned on through a series of reactions initiated by the presence of insulin, it works to drive growth. But it also has a second regulatory function.
When an organism "overfeeds," S6K1 becomes hyperactive, essentially telling insulin to stop bringing more nutrients into the cell. This hyperactive regulation actually results in insulin resistance.
"It would make sense then," said Dr. Thomas, "that once S6K1 tells insulin to stop working, this enzyme would become inactive and its other function of promoting growth would also stop."
But in laboratory studies, Dr. Thomas and his team noticed that mice on high-fat diets continued to grow, even after insulin quit performing its normal function--indicating that S6K1 was still active even after it had seemingly sealed its own fate by shutting down the very trigger that turns it on.