Scientists Discover Mechanism That Protects The Pancreas From Digestion
A team of researchers has unveiled the novel mechanism by which the stress hormone, dubbed as fibroblast growth factor 21 or FGF21, prevents damage to the pancreas by the digestive enzymes.
Published in the journal Cell Metabolism, the study sheds light on the possibility of new therapies for pancreatitis, a potentially life-threatening inflammation of the pancreas.
What Is The FGF21 Stress Hormone?
FGF21 is a stress hormone that stimulates the digestive enzyme secretion and pancreatic juice flow. It also protects the exocrine pancreas from proteotoxic stress.
This metabolic stress hormone is highly expressed in exocrine pancreas, despite the fact that the function of this part of the pancreas is still unknown. The researchers found that the stress hormone, however, stimulates digestive enzyme secretion from pancreatic acinar cells through the autocrine or paracrine mechanism. This mechanism requires signaling through a tyrosine kinase receptor complex, the researchers said.
The Unexpected Role
"Previous studies had shown that FGF21 protected the pancreas, but it was unknown how or by what mechanism," Dr. David Mangelsdorf, lead author of the study, said in a press release.
"We found that FGF21 has a novel, unexpected role in stimulating the pancreas to secrete digestive enzymes into the intestine," he added.
The researchers found another surprising effect of FGF21 - when produced in the liver, it works on the central nervous system like a hormone. However, the FGF21 made in the pancreas works locally that affects only the organ.
Normally, the pancreas creates enzymes that remain inactive, called zymogen granules, until they travel through the pancreatic ducts and go into the intestine, where they become activated to help digest food. When the pancreatic ducts are blocked, the zymogen granules get activated inside the pancreas and they will eventually digest the organ itself.
In one experiment the researchers conducted, they found that mice, which are genetically unable to make FGF21, overproduced zymogen granules in the pancreas. However, the effect was reversed when the mice models received FGF21 infusions. In a second experiment, the researchers discovered that mice genetically engineered to produce FGF21 in excessive amounts were protected from injury when exposed to a pancreatic toxin.
"FGF21 has remarkable pharmacologic effects," Dr. Mangelsdorf said.
"This study suggests an intriguing role in the body's reaction to stresses in the digestive system, but there is more work to be done," he added.