Researchers at the Perelman School of Medicine at the University of Pennsylvania have discovered how to eradicate the risk of weight gain from a certain type of diabetes medication. This means that more patients with diabetes may receive treatment from modified thiazolidinediones, which many likely avoid in their current form due to side effects. These findings have been published inGenes & Development.
According to study senior authorMitchell Lazar, MD, PhD, and the Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases at Penn. Our findings suggest a way to improve the effectiveness of thiazolidinedione medications, which provides an excellent strategy to reduce the side effects of weight gain.
The popularity of diabetes drugs called thiazolidinediones, which are also known as glitazones, has been reduced due to side effects such as weight gain. Interestingly, researchers at Penn discovered that activating just PPAR2 with a thiazolidinedione tablet protects mice against diabetes-like metabolic reactions.
Type 2 diabetes is characterized by the progressive dysregulation of the insulin hormone signaling system in the body, resulting in chronic, high blood pressure, heart attacks, and other chronic diseases. Despite obesity, poor eating habits, and widespread sedentary lifestyles, type 2 diabetes has become a common condition in many countries. It is thought to stem from the establishment of 35 million people in the United States alone, involving roughly 10% of the population.
Thiazolidinediones, which include rosiglitazone, were introduced in the 1990s and, for many years, became widely used as diabetes drugs. These drugs have since become less popular due to side effects. This has led several researchers to investigate whether they might be developed new compounds that retain these drugs therapeutic properties while having fewer side effects.
By looking at the thiazolidinediones target, PPAR, which helps in control fat cell production, Lazar and his team analyzed two lines of mice: one greatly deficient in one form of the protein, PPAR1, and the other significantly deficient in PPAR2. In the mice, scientists showed that activating PPAR1 or PPAR2 with a thiazolidinedione had an anti-diabetic effect in each case, protecting mice from the harmful
However, researchers discovered that activation of these two forms has significant differences downstream impacts on gene activity. Specifically, in the PPAR1-deficient mice (in which the majority of the current PPAR takes the form of PPAR2), the thiazolidinedione therapy caused no weight gain.
This finding suggests that thiazolidinediones may be possible to realize the advantages without the side effects of weight gain, by activating only PPAR2 and not PPAR1.
We are now contemplating in more depth how PPAR1 and PPAR2 work and how they differ, in the hope of finding solutions to selectively activate PPAR2, according to Lazar.