New Insights into Amylin Receptors May Lead to Advanced Weight Loss Medications

Amylin, a hormone that helps regulate appetite and blood sugar by stimulating three distinct receptors in the brain, may be key to developing next-generation obesity treatments. A recent study from the University of Oklahoma published in Science Signaling has revealed important new details about how these amylin receptors react when activated—a breakthrough that could pave the way for more effective drug development.

The senior author of the paper, Augen Pioszak, Ph.D., an associate professor of biochemistry and physiology at the University of Oklahoma College of Medicine, said: "This research presents new biochemical and pharmacological methods we've developed that allow us, for the first time, to determine precisely how drugs in development interact with each of the three amylin receptors."

"Amylin receptors are complex and each has unique properties. Our discoveries could significantly advance drug development efforts in this field," Pioszak noted.

Amylin is released by the pancreas alongside insulin after a meal. Amylin receptors in the brain belong to the same family as GLP-1 receptors, which are targeted by leading-edge drugs such as semaglutide (Ozempic and Wegovy).

"There's considerable interest in developing new obesity medications," said Sandra Gostynska, a doctoral student in Pioszak's lab who is the lead author of the study. "Our work provides the field with new tools to understand how drugs can influence amylin receptors."

Their research has two key findings:

• While all three amylin receptors share a common core component, they have different accessory subunits—suggesting they resemble items of clothing styled differently. Understanding how to specifically target these unique accessories might be crucial for developing drugs that most effectively control appetite and promote weight loss with minimal side effects. Gostynska developed a lab procedure to achieve this insight.
• Drugs may influence the receptors by either drawing their subunits together or spreading them apart, which could also impact how they function and differ from one another in terms of effectiveness.

Pharmaceutical companies are already working on amylin-based drugs. Pioszak mentioned that his lab's research clarifies what happens when these receptors are targeted by medications.

"We believe our findings will enhance drug studies because pharmaceutical and biotech companies need to know how their drug affects each specific amylin receptor," Pioszak said. "Now, we have a method for answering those questions that were previously impossible to resolve."