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By discovering subtle differences between two variants of a protein, researchers at the Perelman School of Medicine at University of Pennsylvania may have figured out how to eliminate a certain diabetes drug that causes weight gain risk
"A small, undiscovered difference between two forms of a single protein turned out to be extremely important," said the study's senior author Mitchell Lazar, Ph.
The popularity of diabetes drugs called thiazolidinediones, also known as glitazones, has been reduced by side effects such as weight gain
Type 2 diabetes is characterized by progressive dysfunction of the body's insulin hormone signaling system, resulting in chronically high levels of glucose (sugar) in the blood
Thiazolidinediones, which include rosiglitazone (brand name Avandia), were introduced in the 1990s and have been widely used for years as a treatment for diabetes
In their study, Lazar and his team addressed this question by further investigating the target of thiazolidinediones, PPARγ, which helps control the production of fat cells
However, the researchers found that activating the two forms had subtly different downstream effects on gene activity
Thus, this finding suggests that by activating only PPARγ2 but not PPARγ1, thiazolidinediones may achieve their benefits without the side effects of weight gain
"We are now studying in more detail how PPARγ1 and PPARγ2 work and how they differ, hoping to find ways to selectively activate PPARγ2," Lazar said
