The protein that keeps the pancreas from digesting itself
Every day, your pancreas produces about one cup of digestive juices, a mixture of molecules that can break down the food you eat. But if these powerful molecules become activated before they make their way to the gut, they can damage the pancreas itself — digesting the very cells that created them, leading to the painful inflammation known as pancreatitis, and predisposing a person to pancreatic cancer.
Now, Salk scientists report in the journal Gastroenterology on April 21, 2022 that a protein known as estrogen-related receptor gamma (ERR ɣ) is critical for preventing pancreatic auto-digestion in mice. Moreover, they discovered that people with pancreatitis have lower levels of ERR ɣ in cells affected by this inflammation.
These findings suggest that new therapies aimed at regulating ERR ɣ activity could help prevent or treat pancreatitis and pancreatic cancer.
“Our finding provides new insight into both the basic biology of how pancreas cells function, and what might drive pancreatitis and pancreatic cancer,” says Professor Ronald Evans, director of Salk’s Gene Expression Laboratory, March of Dimes Chair in Molecular and Developmental Biology, and co-senior author of the study.
The pancreas is home to two main cell types with distinct functions: beta cells that release insulin to control blood sugar levels and acinar cells that produce digestive juices. Evans and his colleagues previously discovered that ERR ɣ helps pancreatic beta cells release insulin and might be useful as a treatment for diabetes. In follow-up studies, the team also discovered that mice lacking ERR ɣ developed severe pancreatitis.
To understand the role of ERR ɣ in pancreatic acinar cells, the researchers compared mice, as well as isolated cells, with and without the protein. They discovered ERR ɣ is required for the functioning of the acinar cells’ mitochondria — organelles that generate energy.

