New Research on Amylin Could Pave the Way for Next-Generation Obesity Drugs

Amylin, a hormone that regulates appetite and blood sugar by activating three distinct brain receptors, might be the foundation for the next generation of obesity drugs. A University of Oklahoma study published today in the journal Science Signaling shows a new understanding of how amylin receptors behave when triggered, a breakthrough that will be critical in drug development. 

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This paper  shows the new biochemical and pharmacological methods we developed that will enable the field, for the first time, to understand exactly what drugs in development do at each of the three amylin receptors. Amylin receptors are very complicated, and each has very different and unique properties. What we have discovered has eluded researchers for many years, and we believe our findings will advance drug development.

Augen Pioszak, PhD, Study Senior Author and Associate Professor, Biochemistry and Physiology, College of Medicine, University of Oklahoma

Following a meal, the pancreas secretes amylin and insulin. Amylin receptors in the brain are related to GLP-1 receptors, which are targeted by new drugs such as semaglutide (Ozempic and Wegovy).

There has been a lot of interest in the pharmaceutical industry for developing new obesity drugs. What we have done is given the field new tools for understanding how a drug can affect amylin receptors.

Sandra Gostynska, Study Lead Author and Doctoral Student, University of Oklahoma

Their results are twofold:

• Although the three amylin receptors have various accessory subunits, they share a fundamental component. It is as though they dress alike but accessorize differently to create unique looks. Developing a medication that best regulates appetite, causes the most significant weight loss, and has the fewest adverse effects may require understanding how to target that uniqueness. To get that realization, Gostynska created a laboratory process.
• Drugs can either bring subunits together or separate them. This might be essential for drug development since drugs may behave differently depending on whether they push or pull.

Pharmaceutical companies are already developing amylin-based drugs. Pioszak said his lab’s research sheds light on what happens when a drug hits a complex network of receptors.

“We believe our findings will further the study of drugs because what pharmaceutical and biotech companies want to know is what their drug does at each amylin receptor. Now we have a method of answering those questions that were previously unanswerable,” added Pioszak.