Furin Steps Into the Spotlight: A Surprising Backup System for GLP-1 Production
Dr. Peter Light
Type 2 diabetes is one of the most common chronic health problems in the world. For millions worldwide, it can feel like a Shakespearean tragedy that never seems to end. Yet, much like our favorite plays, the protagonist of the story - the human body - continues to deliver plot twists in how it avoids a troublesome fate, surprising even the scientists who study it. One such twist lies in how the body copes when a key molecule needed for blood sugar control suddenly goes missing.
Let’s rewind a few scenes to set the stage.
Inside the human gut, long before a person feels full or their blood sugar rises, a performance begins. Specialized hormone-producing cells in the intestine create GLP-1, a hormone famous for helping control blood sugar, boosting insulin release, and signaling fullness so we don’t overeat. In many ways, GLP-1 is our superhero character. It’s the same natural hormone behind today’s most talked-about diabetes and weight-loss medications, including Ozempic and Wegovy.
But GLP-1 doesn’t enter the stage ready to act. It begins as a larger, inactive protein called proglucagon, which must be precisely cut to produce active GLP-1. Normally, this delicate job belongs to a single star enzyme: PCSK1 (proprotein convertase subtilisin/kexin type 1). For decades, PCSK1 has been viewed as the most critical character in making GLP-1. The enzyme knows exactly where and how to slice proglucagon protein into its final, functional form, GLP-1.
Scientists long believed that without PCSK1, GLP-1 would not be made - leaving the body in a precarious position. Without GLP-1, controlling blood sugar is much more difficult.
But a recent study by Dr. Janyne Koepke in Dr. Peter Light’s lab at the University of Alberta revealed a plot twist in the story no one expected. Another character steps out from behind the curtains to save the day and keep GLP-1 alive.
It’s name is: furin.
A Hidden Hero Waiting in the Wings
This overlooked enzyme is well known for cutting many other proteins in the body, such as proteins involved in cell growth, immunity, and even viral activation. But it usually works far from the place where hormones like GLP-1 are made in the gut. However the Light lab had recently shown that GLP-1 can also be made in pancreatic islet cells called alpha cells. They then asked whether PCSK1 was the enzyme responsible? To their surprise, there was no PCSK1 present in alpha cells.
So the Light lab asked a bold question:
If PCSK1 is not involved then perhaps furin could make GLP-1 if only it were in the right place?
The team changed the plot, showing that furin seemed perfectly placed to process GLP-1 in alpha cells. It was like putting a character from one of the tragedies and placing them in a comedy. Imagine Romeo’s best friend, Mercutio, suddenly teleported into Much Ado About Nothing! Furin was not only found in these cells but it was located exactly in the right place to produce active GLP-1. The hormone was properly cut, fully functional, and capable of activating the same insulin-boosting and glucose-regulating pathways as natural GLP-1.
Furin doesn’t just help the production of GLP-1…it plays a starring role.
A New Perspective on Diabetes and Human Biology
This discovery reshapes how scientists think about GLP-1 production. It may explain why some people with PCSK1 mutations still produce GLP-1. More importantly, it opens the door to new strategies for increasing GLP-1 levels naturally, offering new hope for future diabetes treatments.
By showing that furin, previously assumed to play no role, actually plays a starring role. The Light lab has revealed an important new insight into how the body maintains key hormonal signals.
It is a reminder that in science, just like in theatre, a new and unexpected character may hold the power to change the ending of the story.