Scientists Discover Mechanism by Which Stress Hormone FGF21 Protects Pancreas from Digestive Enzymes; Finding May Lead to New Therapies for Pancreatitis, a Key Adverse Effect of Alcoholism

University of Texas (UT) Southwestern Medical Center researchers have uncovered the mechanism by which the stress hormone FGF21 keeps digestive enzymes from damaging the pancreas. The research, published online on January 12, 2017 in Cell Metabolism, points to the possibility of new therapies for pancreatitis, a potentially life-threatening inflammation of the pancreas. The article is titled “FGF21 Is an Exocrine Pancreas Secretagogue.” Pancreatitis can have many causes, including heavy, long-term alcohol drinking, gallstones, and certain hereditary conditions. Approximately 210,000 U.S. residents are hospitalized with acute pancreatitis annually, according to the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases. Dr. David Mangelsdorf (left in photo) and Dr. Steven Kliewer (right in photo) – who have run a joint laboratory at UT Southwestern since 2002 – earlier reported that the liver hormone FGF21, or fibroblast growth factor 21, acts via the brain’s reward pathway to reduce the desire for sugar and alcohol in mammals. In November 2016, they published a collaborative study with European researchers comparing the genomes of more than 105,000 light and heavy social drinkers. That investigation identified a gene variant for the brain’s FGF21 receptors that suppresses the desire to drink alcohol. The researchers then turned their attention from FGF21’s effects in the central nervous system to the digestive system, where another mystery awaited. “Previous studies had shown that FGF21 protected the pancreas, but it was unknown how or by what mechanism,” said Dr. Mangelsdorf, Chair of Pharmacology and a Howard Hughes Medical Institute Investigator.
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