JDRF-Funded Researchers from Two Universities Separately Discover the Links between Cell Stress, Inflammation, and Beta Cell Death in Diabetes
--Researchers from Washington University School of Medicine in St. Louis and the University of California, San Francisco publish concurrent results in the same August edition of Cell Metabolism--
New York, NY, August 7, 2012--When JDRF-funded research teams from two separate universities met three years ago, they learned that they were on similar paths in their attempt to discover the link connecting beta cell stress with inflammation and beta cell death in type 1 diabetes (T1D). Rather than racing to be the first to reveal preliminary findings, however, the teams from the University of California, San Francisco (UCSF), and Washington University School of Medicine in St. Louis decided that their cooperation would provide a more comprehensive understanding of the basis of the disease and would thus be more beneficial to diabetes research. The two labs moved forward with their separate studies, communicating regularly to exchange new findings. In the end, both teams had independently discovered how the beta cell protein TXNIP links cell stress with inflammation and cell death. Both studies will be published in the August 8th print edition of Cell Metabolism, and are available online (www.cell.com) from today.
"Inflammation is a major factor in the death of insulin-producing beta cells during the progression of type 1 diabetes; however, the mechanisms initiating inflammation in type 1 diabetes were elusive," said Fumihiko Urano, M.D., Ph.D., primary investigator of the study at Washington University. "We discovered that beta cell stress plays an important role in the initiation of inflammation through TXNIP."
In T1D, a person's immune system attacks and destroys insulin-producing beta cells in the pancreas, causing insulin dependence. Researchers previously found that prior to the onset of diabetes, the body's demand on beta cells to secrete more insulin creates a stressful environment within the cellular compartment known as the endoplasmic reticulum (ER), causing what is known as ER stress. These prior studies showed that ER stress, if left too high, leads to beta cell death. The researchers from UCSF and Washington University discovered that ER stress itself provokes an inflammatory response, and as attempts at cell repair fail, the beta cells are actively pushed toward cellular suicide.
"In one of the paradoxes of biology, living cells will often take a stressful situation and actively make it worse," said Feroz Papa, M.D., Ph.D., primary investigator of the study at UCSF. "We also found that the connecting link between ER stress and inflammation is a protein called TXNIP, and that genetically removing TXNIP prevented a form of diabetes caused by ER stress. We believe that shutting off ER stress signaling and inflammation directly at its beginning source, may perhaps lead to new treatments for type 1 diabetes."
"JDRF is excited by these studies because this knowledge may be exploited to discover drugs to block the beta cell suicide process, and by doing so, prevent beta cell loss and restore beta cell function and health," said Patricia Kilian, Ph.D., director of JDRF's beta cell regeneration program. "The replication of these findings by two separate laboratories greatly increases our confidence that this is an important step toward achieving the goal of ending beta cell destruction."
JDRF-funded investigators in these studies and at other institutions are actively pursuing efforts to enable discovery and development of drugs based on knowledge of the pathways and proteins linking beta cell stress with inflammation and beta cell death for T1D and other forms of diabetes.
In T1D, a person's pancreas stops producing insulin, a hormone that enables people to get energy from food. People with T1D need to test their blood sugar and give themselves insulin (with injections or an insulin pump) multiple times every day, and carefully balance insulin doses with eating and daily activities throughout the day and night. However, insulin is not a cure for diabetes, and even with that intensive care, a significant portion of the day is still spent with either high or low blood sugar, placing people with T1D at risk for devastating complications such as heart attack, stroke, blindness, and amputation.
About the University of California, San Francisco
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. www.ucsf.edu.
About Washington University School of Medicine
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare. http://medicine.wustl.edu/.
JDRF is the leading global organization focused on type 1 diabetes (T1D) research. Driven by passionate, grassroots volunteers connected to children, adolescents, and adults with this disease, JDRF is now the largest charitable supporter of T1D research. The goal of JDRF research is to improve the lives of all people affected by T1D by accelerating progress on the most promising opportunities for curing, better treating, and preventing T1D. JDRF collaborates with a wide spectrum of partners who share this goal.
Since its founding in 1970, JDRF has awarded more than $1.6 billion to diabetes research. Past JDRF efforts have helped to significantly advance the care of people with this disease, and have expanded the critical scientific understanding of T1D. JDRF will not rest until T1D is fully conquered.