The human pancreas is a tricky organ to study. We need it while we are alive to make insulin to help us regulate our blood sugar levels and to help us break down our food for our intestines to absorb. But, being chockfull of digestive enzymes, it doesn't last long after death. Relying on laboratory animals like mice has shed some insight into the organ's function, but it's not been possible to study age-related changes that take place over the decades that make up most people's lives. This is particularly important to diabetes researchers who want to understand the root causes of the disease.
Developmental biologist Seung Kim, MD, PhD has spent the past several years working with colleagues and organ procurement organizations around the country to come up with a way to quickly isolate and analyze pancreatic islet cells from deceased donors of all ages. He and postdoctoral scholar Efsun Arda, PhD, published their findings recently in the journal Cell Metabolism.
As Kim explained in our release:
Pancreatic islets, which are the sites of insulin production, mature and change in their function after a baby is born. We think our findings suggest that this maturation process goes on for nearly a decade. There’s been a growing realization among diabetes researchers that human islet development differs significantly from islet development in typical laboratory animals like mice.
Clearly, the ability to study human tissue is paramount. But this has been difficult to do because the pancreas doesn't last long after death. Kim and his colleagues worked for six years to organize and implement a process to collect and analyze pancreatic tissue shortly after death from human organ donors spanning the ages of six months to 66 years. They were able to identify patterns of gene expression in the islet cells of the donors that varied with age.
"This is a unique and valuable resource for researchers wishing to begin to understand how gene expression is dynamically regulated in human islet cells," Kim said. "Our study charts a new road map for researchers working to use stem cells to replace human islet cells by highlighting changes that normally occur and should perhaps be taken into consideration when analyzing cells for transplant."
Using the data, the researchers identified two genes whose expression increases in islet cells as a person ages. Increasing the expression of one of the proteins, SIX3, in the insulin-producing cells isolated from younger donors enhanced their ability to respond efficiently to rising glucose levels.
More from our release:
Although [the genes] have not been implicated directly in pancreatic function, genomewide association studies have linked the presence of a mutation near the genes to an impaired ability to properly manage fasting blood-glucose levels.
“This is a tantalizing link,” said Kim. “It appears that genes whose expression changes from childhood to adulthood may be disproportionately associated with an increased risk for diabetes.”
The researchers plan to continue their studies of age-related changes in pancreatic function as part of an ongoing, multi-laboratory Stanford focus on diabetes and metabolism research.