US researchers find new method to protect pancreas from digestive enzymes

Researchers from the University of Texas Southwestern Medical Center have identified a new mechanism whereby the stress hormone FGF21 protects pancreas from digestive enzymes.

The research focuses on the possibility of new therapies for pancreatitis, which may be caused due to heavy, long-term alcohol drinking, gallstones, and certain hereditary conditions.

Howard Hughes medical institute investigator Dr Mangelsdorf said: "Previous studies had shown that FGF21 protected the pancreas, but it was unknown how or by what mechanism.

"We found that FGF21 has a novel, unexpected role in stimulating the pancreas to secrete digestive enzymes into the intestine."

As part of the study, it was found that FGF21 works on the central nervous system like a hormone when produced in the liver.

In contrast, FGF21 made in the pancreas acts locally and affects only that organ.

"We found that FGF21 has a novel, unexpected role in stimulating the pancreas to secrete digestive enzymes into the intestine."

The researchers carried out an experiment, observing that mice were genetically unable to make FGF21 overproduced zymogen granules in the pancreas and this effect was reversed when they received FGF21 infusions.

Another experiment revealed that mice genetically engineered to overproduce FGF21 were protected from injury when exposed to a pancreatic toxin and if they lack FGF21 they were more susceptible to damage from the toxin.

FGF21 was initially described in association with dietary stresses such as starvation and high-fat diets, and is also produced when mammals consume carbohydrates and alcohol.

The researchers stressed that any potential therapeutics will need to address some unusual side effects seen in their previous mouse studies, such as bone loss and increased levels of the fight-or-flight hormones known as glucocorticoids.

UT Southwestern’s research received support from the National Institutes of Health, the Robert A. Welch Foundation, a National Science Foundation Graduate Research Fellowship, and the Howard Hughes Medical Institute.

The recombinant FGF21 used in the experiments was provided by Novo Nordisk.