Scientists at Stanford University have identified a pathway responsible for age-related beta cell decline. The long time JDRF-funded researchers have also shown the ability to alter this pathway and coax the older cells into dividing as frequently as they did when they were younger.
The research appeared in the October 12 issue of Nature
and provides the greatest understanding of the molecular and biochemical systems attributed to the halt of beta cell division with age. These findings could encourage more research into the use of beta cell regeneration as a viable treatment for both Type 1 and Type 2 diabetes.
Led by Seung Kim, MD, PhD., the studies showed that the PDGF protein, or platelet derived growth factor, and its receptors send beta cells signals to divide through a pathway that controls the levels of two proteins in the beta cell nucleus – the area where division occurs. Dr. Kim found that PDGF binds to its receptor on the beta cell’s surface and controls the level of these regulating proteins allowing for cell division in the cells of young mice. In older mice, the beta cells were shown to lose these receptors, preventing cell divide. Through the increase of these PDGF receptors, Dr. Kim and his team discovered that they could stimulate the old cells tocontinue division.
Further tests confirmed that this beta cell proliferation pathway is also present within human beta cells. Results showed a similarly direct correlation in human cells between PDGF receptor presence and the development of new cells as was found in mice.
Attempts to rejuvenate beta cell production before the discovery of the PDGF receptors have all been met with little success. "You can get these cells to grow but they will literally lose their specific identity as a beta cell," Dr. Kim says. "They will either stop making insulin, or they'll grow just fine but they will grow uncontrollably or into other cell types."
"With these advanced technologies, we are now able to get a comprehensive view-at the genetic level-of the changes beta cells undergo as they age, and we can track these changes and study them in a systematic way," he continues. "By understanding what genes are turned on and off in a young beta cell, we can try to recreate that genetic environment in older beta cells such that they divide in a desirable, controlled manner."
This greater understanding of PDGF receptors and their relationship with beta cell production could enable researchers to discover new effective methods of replacing lost beta cells and treating diabetes.