An international group of U.S. and Korean researchers have discovered the protein that regulates the activity of digestive enzymes produced by the acinar cells in the pancreas in order to break down the food that we eat.
The protein, estrogen-related receptor gamma (ERR-gamma), helps to stop these enzymes becoming active before they reach the gut. In some pancreatic diseases, these enzymes can activate abnormally early and cause damage to the pancreas, which is linked to problems with cellular energy supply from the mitochondria.
“Our finding provides new insight into both the basic biology of how pancreas cells function, and what might drive pancreatitis and pancreatic cancer,” said Professor Ronald Evans, director of the Salk Institute’s Gene Expression Laboratory, and co-senior researcher on the study, in a press statement.
There are two main types of cells in the pancreas. Perhaps more well-known are the beta cells that release insulin and are damaged in individuals with diabetes. Acinar cells, in contrast, produce digestive enzymes that help to digest different types of food.
ERR-gamma was previously discovered by Evans and colleagues, as it also plays a role in helping pancreatic beta cells release insulin. They also noted that mice lacking ERR-gamma developed severe pancreatitis and that abnormally low levels of this protein are present in people with pancreatitis.
As described in the journal Gastroenterology, in this study the team investigated the activity of ERR-gamma further and found it also regulates how and when digestive enzymes are activated. They compared two mouse models and a pancreatic cell line with and without ERR-gamma, as well as looking at human pancreatic biopsies, to better assess its function. They found that the energy giving mitochondria, which fuel the activity of the pancreatic acinar cells, cannot function without ERR-gamma.
“Mitochondria have been known to be the major source of energy in acinar cells since the 1960s, but the factor that controls this vital energy production program in acinar cells has been a long-standing mystery,” said co-senior author Jae Myoung Suh of the Korea Advanced Institute of Science and Technology (KAIST), in South Korea.
The lack of a functional energy source causes dysfunctional activity in the acinar cells, which incorrectly activate digestive enzymes that start to digest the pancreatic cells and cause damage. This damage can cause symptoms of pancreatitis and also makes cancerous cell conversion more likely.
The research team hope this finding and potential new target can help to drive development of more effective treatments for pancreatitis and pancreatic cancer, which are sorely needed.