Rediscovering the Value of an Outdated Diabetes Drug

Researchers at the University of California – San Diego have recently unlocked the biochemical mechanisms behind an old diabetes drug, paving the way for the development of new, safer therapeutic alternatives. Published in Nature Metabolism, their findings could revolutionize how type 2 diabetes is treated, with potential treatments that avoid the problematic side effects of earlier drugs.

Rediscovering the Value of an Outdated Diabetes Drug 1

The Old Meets the New in Diabetes Treatment

Thiazolidinediones (TZDs), once the cornerstone of type 2 diabetes treatment in the 1990s and early 2000s, fell out of favor due to their adverse effects, including weight gain and fluid retention. Despite their decline, these drugs are unique in their ability to reverse insulin resistance—a primary factor in type 2 diabetes.

At UC San Diego School of Medicine, researchers have taken a fresh look at TZDs to understand how they can retain their beneficial properties while eliminating negative side effects. Dr. Jerrold Olefsky, a professor of medicine and assistant vice chancellor for integrative research at UC San Diego Health Sciences, explained the importance of their research. “Impaired insulin sensitivity is the root cause of type 2 diabetes, so any treatment we can develop to safely restore this would be a major step forward for patients,” he said.

A Breakthrough in Understanding and Application

The research team’s exploration into the molecular workings of TZDs led to significant findings using rosiglitazone, a well-known TZD. They discovered that while treated obese mice became more insulin-sensitive, they also experienced the known negative side effects. To circumvent these, the researchers isolated exosomes—tiny capsules containing microRNAs that regulate gene expression—from the adipose tissue macrophages of treated mice. Injecting these exosomes into another group of untreated obese mice replicated the positive effects of rosiglitazone without the undesirable outcomes.

The exosomes were just as effective in reversing insulin resistance as the drug itself but without the same side effects,
Olefsky highlighted, indicating a new pathway by which obesity-related inflammation could be linked to diabetes.

MicroRNAs: The Future of Diabetes Treatment?

Further analysis revealed that a specific microRNA within the exosomes, called miR-690, was responsible for the beneficial metabolic effects. While using exosomes as a direct treatment might be impractical due to production and administration challenges, understanding their role at the molecular level opens possibilities for new drugs that can mimic these effects.

“There’s also plenty of precedent for using microRNAs themselves as drugs, so that’s the possibility we’re most excited about exploring for miR-690 going forward,” Olefsky added, outlining the potential future of diabetes treatment inspired by the actions of an outdated drug. This old diabetes medication, while no longer favored, still has valuable lessons to teach about safer, more effective diabetes management.

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