The pancreas is one of the most important organs in the body. It produces insulin to help regulate blood sugar and help digest food. When the pancreas becomes disordered, diabetes, cancer or other diseases threaten life.
However, much is still unknown about how the pancreas keeps people healthy and how the organ can fail. Tens of thousands of proteins control how the pancreas works: how it grows and develops, how it produces digestive enzymes, and how it secretes insulin. Scientists need to know how this protein landscape changes over time in order to develop treatments for diabetes or cancer.
“Traditionally, researchers may have studied individual proteins. But no single protein can work on its own. The goal is to get a more complete picture of all the proteins involved, ”says Lingjun Li, professor of chemistry and pharmacy at the University of Wisconsin – Madison, who led new research to measure the entire pancreatic protein suite.
“These basic data help people who work on various pancreatic diseases such as pancreatitis, pancreatic cancer or diabetes,” says Li.
Working with transplant surgeon Jon Odorico’s lab at the UW School of Medicine and Public Health, Li’s research group tracked changes in the pancreatic proteome – the entire set of proteins – from pre-birth to late adulthood. The team also examined the extracellular matrix, an understaffed network of supportive proteins that bind cells together. The extracellular matrix is important for the growth and support of pancreatic cells in the laboratory and during transplantation.
The study showed that the pancreas significantly rearranged its proteins throughout childhood and eventually stabilized in adults. Age-specific changes were seen in cancer-linked proteins in particular, which should help researchers refine their understanding of pancreatic cancer.
The scientists published their work on February 15 in the journal Nature Communications.
To measure the pancreatic proteome, the research team turned to mass spectrometry, a technology that identifies thousands of different proteins based on their unique molecular weights and sequences. The laboratory developed an inexpensive set of distinguishable tags that were attached to proteins from different tissue samples so that multiple samples could be run at the same time, to speed and simplify the data acquisition process.
The pancreas samples were from organ donors aged 5 to 61 years when the tissue was not suitable for transplantation but was otherwise healthy and from donated fetal tissue. These decades of tissue collection provided an opportunity to see how the pancreas changes over the course of life.
“Many proteins related to pancreatic function become more common with age, including disease-related biomarkers,” said Zihui Li, co-lead author of the new report and a PhD student in Li’s lab. “In many previous studies, these biomarkers were only identified as being related to disease progression. Now we know that you need to consider the influence of age when assessing the importance of these biomarkers.”
In a work led by Dan Tremmel, PhD student in the Odorico laboratory and co-lead author of the study, the researchers were able to determine the positions of extracellular matrix proteins and determine that the proteins also change significantly over the course of life.
“I think the broad takeaway message that is really interesting is that there are so many changes in these extracellular matrix proteins. It’s a very dynamic system as it evolves, ”says Tremmel, who notes that the work is important for transplant researchers, especially those dealing with diabetes.
Pancreatic islet cells produce insulin, and their malfunction leads to diabetes. Information about the location and protein remodeling of extracellular matrix proteins can be used by the Odorico group and others to better aid research with pancreatic islet cells and the transplantation of these cells in people with the disease.
The laboratories created an extensive dataset that is unique in that it studies the pancreas’ key proteins for almost a lifetime and focuses on healthy tissue, not diseased tissue. Now other scientists can access the entire dataset to improve their own research.
“The entire study really deals with details that have not been previously identified and shown. Other people can use this information to optimize their studies in their own way, ”says Sara Sackett, a scientist at the Odorico laboratory.
This access to new information, both for her own work and for others in the field, kept Li excited about the future.
This work was supported in part by the National Institutes of Health (grants R21AI126419, R01DK071801, RF1AG052324, P41GM108538, 1F31DK125021-01, UL1TR002373, and S10RR029531).