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The pancreas is one of the most important organs in the body. It produces insulin to regulate blood sugar and helps digest food. If the pancreas goes haywire, diabetes, cancer, or other illnesses threaten lives.
Yet, much remains 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 to help develop treatments for diabetes or cancer.
“Traditionally, researchers may have looked at individual proteins. But no protein can work on its own. The goal here 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 has helped lead new research measuring all of the protein range of the pancreas.
“Having this basic data will help people who are working on different pancreatic diseases like pancreatitis, pancreatic cancer or diabetes,” Li says.
Working with the UW Medical School lab and public health transplant surgeon Jon Odorico, Li’s research group has been tracking changes in the pancreatic proteome – its complete set of proteins – from birth. at the end of adulthood. The team also studied the extracellular matrix, an under-researched network of supporting proteins that bind cells together. The extracellular matrix is vital for the growth and support of pancreatic cells in the laboratory and during transplants.
The study showed that the pancreas significantly remodels its proteins throughout childhood, eventually stabilizing in adults. In particular, age-specific changes have been pronounced among cancer-related proteins, a finding that 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 by their molecular weights and unique sequences. The lab developed a cost-effective set of separate labels that they attached to proteins from different tissue samples, allowing them to analyze multiple samples at a time to speed up and simplify the data collection process.
Pancreatic samples were from organ donors aged 5 to 61, when the tissue was unsuitable for transplantation but was otherwise healthy, and donated fetal tissue. This collection of tissues spanning decades has provided a chance to see how the pancreas changes throughout life.
“Many proteins related to pancreatic function show increasing abundance with age, including disease-related biomarkers,” says Zihui Li, lead co-author of the new report and graduate student of Li’s lab. Previous studies only identified these biomarkers as being related to disease progression, but now we know you need to consider the effect of age when assessing the importance of these biomarkers. ”
In work led by Odorico Lab graduate student and study co-lead author Dan Tremmel, researchers were able to identify the locations of extracellular matrix proteins and found that proteins also change dramatically throughout. of life.
“I think the big takeaway message that’s really interesting is that there are so many changes in these extracellular matrix proteins. It’s a very dynamic system during development, ”says Tremmel, who notes that the work is important for transplant researchers, and especially those focusing on diabetes.
Pancreatic islet cells produce insulin and their dysfunction leads to diabetes. Information on the location and protein remodeling of extracellular matrix proteins can be used by the Odorico group and others to better support research on pancreatic islet cells, and when transplanting these cells into people. with the disease.
The labs have produced a rich data set that is unique as it examines the most important proteins in the pancreas over almost a lifetime and focuses on healthy tissue, as opposed to diseased tissue. Now other scientists can access the dataset to improve their own research.
“The whole study really digs into details that haven’t been identified and shown before. Other people can use this information to refine their studies in their own way, ”explains Sara Sackett, scientist at the Odorico laboratory.
This access to new information, both for his own work and for others in the field, has thrilled Li for the future.
This work was supported in part by the National Institutes of Health (grants R21AI126419, R01DK071801, RF1AG052324, P41GM108538, 1F31DK125021-01, UL1TR002373 and S10RR029531).
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