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¡Xas they are in type 1 diabetes¡Xtreatment with the hormone insulin becomes essential to regulate blood glucose levels and get energy from food. Now, longtime JDRF-funded researchers at Stanford University have identified a pathway responsible for this age-related decline, and have shown that they can tweak it to get older beta cells to act young again¡Xand start dividing.
The work, to appear in the October12 issue of Nature, 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 Seung Kim, M.D., Ph.D., 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, Dr. 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. Dr. Kim and his colleagues 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.
In the past, researchers have used other techniques to trigger older beta cells to start dividing, but they have been met with challenging results, explains Dr. Kim, who is also a Howard Hughes Medical Institute investigator. "You can get these cells to grow but they will literally lose their specific identity as a beta cell," he says. "They will either stop making insulin, or they'll grow just fine but they will grow uncontrollably or into other cell types."
But with the advent of better genetic tools and the completion of the human genome project, that era has come to pass, he explains. "With these advanced technologies, we are now able to get a comprehensive view¡Xat the genetic level¡Xof 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."
By better understanding the mechanisms that control and govern pancreatic ƒÒ-cell proliferation, researchers could transform treatments for diabetes. The cascade leading from PDGF binding to its receptor on the beta cell's surface to changes in protein levels within the nucleus could inspire scientists with new ideas on how to discover new drugs to safely promote beta cell regeneration to replace those lost in diabetes.
"A major goal of JDRF's regeneration program is to find ways to preserve and restore functional beta cells as a cure for type 1 diabetes. One of the challenges is that adult beta cells do not readily replicate, and these new findings provide key insight on how the body regulates beta cell growth and replication," says Patricia Kilian, Ph.D., JDRF's scientific program director of regeneration research. "Based on these key scientific insights, we hope the new findings will help enable the discovery of safe therapies to promote beta cell regeneration."
JDRF is the worldwide leader for research to cure type 1 diabetes (T1D). It sets the global agenda for diabetes research, and is the largest charitable funder and advocate of diabetes science worldwide.
The mission of JDRF is to find a cure for diabetes and its complications through the support of research. T1D is an autoimmune disease that strikes children and adults suddenly, and can be fatal. Until a cure is found, people with T1D have to test their blood sugar and give themselves insulin injections multiple times or use a pump--each day, every day of their lives. And even with that intensive care, insulin is not a cure for diabetes, nor does it prevent its potential complications, which may include kidney failure, blindness, heart disease, stroke, and amputation.
Since its founding in 1970 by parents of children with T1D, JDRF has awarded more than $1.5 billion to diabetes research, including $107 million last year. More than 80 percent of JDRF's expenditures directly support research and research-related education. For more information, please visit www.jdrf.org.
Joana Casas | EurekAlert!
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News