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Older Beta Cells Act Young Again
With advancing age, insulin-
producing beta cells divide
infrequently (above). By activating
the PDGF pathway, researchers
can coax these older beta cells
to divide as they did when they
were young (down);© JDRF
As a person ages, the ability of their beta cells to divide and make new beta cells declines. By the time children reach the age of 10 to 12 years, the ability of their insulin-producing cells to replicate greatly diminishes. If these cells, called beta cells, are destroyed - as they are in type 1 Diabetes - treatment with the hormone insulin becomes essential to regulate blood glucose levels and get energy from food.
The work provides the most complete picture to date of the molecular and biochemical mechanisms that bring beta cell regeneration to a near halt as beta cells age. These findings may help pave a path for developing strategies to restore beta cell number to treat both type 1 and type 2 Diabetes.
In their work, the researchers, led by Doctor Seung Kim of Stanford University, found that a protein called PDGF, or platelet derived growth factor, and its receptor send beta cells signals to start dividing via an intricate pathway that controls the levels of two proteins in the beta cell nucleus, where cell division occurs. Working with young mice, Kim and his team found that PDGF binds to its receptor on the beta cell's surface and controls the level of these regulating proteins allowing cells to divide. However, in older mice, they discovered that beta cells lose PDGF receptors, and that this age-related change prevents beta cells from dividing. The scientists further found that by artificially increasing the number of PDGF receptors, they can restore the ability of the beta cell to divide and generate new cells.
The researchers also show that this age-dependent beta cell proliferation pathway is also present in human beta cells. Similar to the findings with mice beta cells, the researchers found that juvenile human islet beta cells proliferate in response to PDGF, but adult human islet beta cells do not due to a reduced level of PDGF receptors.
With the advent of better genetic tools and the completion of the human genome project, that era has come to pass, Kim explains. "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 adds. "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."
MEDICA.de; Source: JDRF Juvenile Diabetes Research Foundation International