Under special conditions, some cells of the pancreas can produce the hormone GLP-1, mimicked by popular diabetes drugs like Ozempic and Wegovy, according to a new study that upends what we knew about the organ.
Until now, the alpha cells of the pancreas were thought to only produce the molecule glucagon, and not GLP-1, which is typically made in the gut.
Now, a new study by Duke University researchers reveals that when glucagon production is blocked, they can also “switch gears” to produce GLP-1 and even amp up its levels, enhancing insulin release and blood sugar control.
The findings, published in the journal Science Advances, confirm that alpha cells in the pancreas can also release GLP-1 into the bloodstream after eating, helping to lower blood sugar by increasing insulin.
This points to a surprising new ally in the fight against type 2 diabetes, researchers say.
In the study, scientists analysed pancreatic tissue from both mice and humans across a range of ages, body weights, and diabetes statuses.
When they blocked glucagon production in the mouse pancreas, they hoped insulin levels would drop.
However, researchers found that the apha cells switched gears, ramping up GLP-1 production, which improved glucose control and triggered a stronger insulin release.
They found that human pancreatic tissue produced much higher levels of bioactive GLP-1 this way, which was directly linked to insulin secretion.
"This research shows that alpha cells are more flexible than we imagined...They can adjust their hormone output to support beta cells and maintain blood sugar balance,” said Jonathan Campbell, an author of the study from Duke University.
Scientists hope this flexibility could be leveraged to treat type 2 diabetes, where beta cells in the pancreas can't make enough insulin to keep blood sugar at a healthy level.
By boosting the pancreatic GLP-1 production, researchers hope it could offer a more natural way to support insulin and manage blood sugar.
To test this further, scientists manipulated two enzymes – PC2, which drives glucagon production, and PC1, which produces GLP-1.
When they blocked PC2, it boosted PC1 activity and improved glucose control.
However, when both enzymes were removed, insulin secretion dropped and blood sugar spiked, confirming the critical role of GLP-1.
Until now, metabolic stressors like a high-fat diet are known to increase GLP-1 production in the pancreatic alpha cells, but only modestly.
If future research can find ways to safely boost GLP-1 output from alpha cells, it could naturally enhance insulin secretion in people with diabetes.
"This discovery shows that the body has a built-in backup plan. GLP-1 is simply a much more powerful signal for beta cells than glucagon,” Dr Campbell said.
“The ability to switch from glucagon to GLP-1 in times of metabolic stress may be a critical way the body maintains blood sugar control,” he explained.
