March 2010 eUpdate
March 5, 2010
Breakthrough Discovery In Beta Cell Development
A recent study involving a previously unstudied gene known as Rfx6 has shown how this gene is necessary for cells to differentiate into insulin-producing beta cells and other cells in the pancreas. This study was led by Michael German, MD , Diabetes Center Clinical Director and the Justine K. Schreyer Endowed Chair in Diabetes Research, and his colleague Constantin Polychronakos, MD, of McGill University. Dr. German and his team found that mice lacking the Rfx6 gene failed to generate most of the normal cells in the pancreas including the beta cells. They also found in humans that the absence of this gene will cause a complete absence of islets, leading to a rare syndrome of neonatal diabetes in infants. Published in the prestigious journal, Nature, this study provides critically important insights for both beta cell development and insulin production. This discovery may also help create new drugs to regenerate beta cells in patients with diabetes. Stuart Smith, PhD in the German Lab was the lead author of this journal article. This research was funded in part by the Juvenile Diabetes Research Foundation.
Unlocking the Secrets of Autoimmunity
It is hard to believe that a single patient can lead to new insights into autoimmune disease that merit publication in the New England Journal of Medicine (NEJM) . In a recent Letter to the Editor in the journal, our DC investigators report the case of a patient seen at the San Francisco General Hospital with symptoms of autoimmune polyglandular syndrome type 1 (APS1). APS1 is a disease characterized by multiple autoimmune disorders, often including type 1 diabetes. As a leader in research on the AIRE gene and APS1, Mark Anderson, MD, PhD , the Robert B. Friend and Michelle M. Friend Endowed Chair in Diabetes Research, was consulted on this case. At first it appeared that this patient had no defect in the AIRE gene that is normally associated with APS1. However, the UCSF team discovered a thymic tumor that showed a defect in AIRE function. Because AIRE normally prevents autoimmune disease by promoting deletion of T cells that recognize self-tissues, the lack of AIRE function in the thymic tumor caused the APS1. Though the development of autoimmunity is complex, the discovery of a molecular link between two uncommon causes of autoimmunity--thymic tumors and APS1--has implications for treating all types of autoimmune disease. It also highlights that acquired problems with the AIRE gene can provoke autoimmunity later in life. An APS1 and Autoimmune Disease Clinical Trial has been launched to further explore these issues of autoimmunity. For more information, contact Mickie Cheng, MD, PhD who also serves as first author on the NEJM publication. [ Public Affairs Story ]
Researchers Recognized at World Insulin Resistance Meeting
At the 7th World Congress on Insulin Resistance , researchers from the UCSF Diabetes Center received awards for their new research involving insulin resistance. Sinan Tanyolac, MD, a UCSF visiting scholar from Istanbul University who works closely with Diabetes Center researchers Ira Goldfine, MD and John Kane, MD , received first place for studies on the genetics of insulin resistance and type 2 diabetes. The team recently identified variants in the protein, High Mobility Group A1 (HMGA1) -- a nuclear transcription factor which plays a critical role in the regulation of the insulin receptor gene. When the HMGA1 expression is down regulated, it causes a reduction of the insulin receptor on the cell surface, impairing the regulation of the insulin signaling pathway thus causing insulin resistance. Of great significance -- the team estimates that 10% of American, Italian and French patients with type 2 diabetes have this HMGA1 variant which predisposes them to insulin resistance. Thus, the HMGA1 gene may serve as a predictive marker of type 2 diabetes. Also honored for their research at this meeting were Jack Youngren, PhD, Umesh Masharani, MD , and Ira Goldfine, MD for their clinical research studying insulin resistance in lean prediabetic subjects. They observed that in these subjects insulin resistance was associated with preferential activation of the muscle JNK stress kinase pathway which inhibits insulin signaling.
CLINICAL RESEARCH
Ten Years of the Immune Tolerance Network
When Dr. Jeffrey Bluestone came to UCSF in 2000, he brought with him an innovative and highly collaborative government-backed project that would help change the face of clinical research -- the Immune Tolerance Network (ITN). The ITN is a multidisciplinary clinical research network that was created in 1999 by the National Institute of Allergy and Infectious Diseases (NIAID), the Juvenile Diabetes Research Foundation (JDRF), and the National Institute of Digestive and Kidney Diseases (NIDDK) with the goal of speeding the clinical development of new treatments for immune tolerance. Targeting transplantation, allergy & asthma and autoimmune diseases like type 1 diabetes, the ITN's success under Dr. Bluestone's leadership has reverberated far and wide, with academic, government and industry researchers around the world now looking to the ITN as a new model for clinical research. The ten year journey of the ITN was recently chronicled and published in the prestigious journal, Science Translational Medicine . This article is available from their website or may be downloaded from the ITN website.
CLINICAL NEWS
New Diabetes Education Program Available for Bay Area Businesses
Bay area employers are concerned about the rising incidence of diabetes in today's society. One of three families are affected by diabetes or at risk for contracting this disease. Providing education on diabetes prevention, warning signs, common myths, and general treatment options is vitally important to keep staff healthy and happy. As a public service to the local business community, the UCSF Diabetes Teaching Center has launched a program offering free, one hour diabetes group instruction to employees. These informational sessions are being led by Peggy Huang, RN, CDE , an accomplished diabetes nurse educator who co-founded the Teaching Center. To sign up your company for this new 2010 program, please contact Lorraine Stiehl. Last year, the Diabetes Teaching Center successfully launched their free, online educational website for the public at large, Diabetes Education Online.
Spotlighting UCSF Transplantation During National Kidney Month
Since March is National Kidney Month and March 11, 2010 is officially World Kidney Day, we'd like to acknowledge the tremendous success of our UCSF Transplantation Program . UCSF has performed more kidney transplants than any other institution in the world — more than 8,300 since 1964 — and is the fifth largest center for living-donor kidney transplants in the country. Each year, the transplant team evaluates about 1,200 patients and performs more than 350 kidney transplants. Our one-year success rate is one of the highest in Northern California and our pediatric kidney transplant program is one of the largest of its kind in the U.S. Additionally, we are also a leader in pancreas and pancreas-kidney transplants for patients with diabetes. Currently we offer three kinds of pancreas transplants: a combined pancreas and kidney transplant for diabetics suffering from end-stage kidney disease (ESRD); a solitary pancreas transplant to prevent the onset of diabetic complications in the kidney, including a previously transplanted kidney; and an islet transplant — to effectively restore insulin independence in patients with diabetes. Since islet transplantation is still considered clinical research, we encourage you to learn about our clinical trials sponsored by the CIT Consortium , an international collaborative effort that is examining outcomes of islet transplantation in type 1 diabetes and evaluating novel immunosuppressive agents in preventing islet rejection. We are also in the process of launching our islet-after-kidney trial . For more information, contact islettransplant@ucsfmedctr.org
NOTES AND NEWS
UCSF Diabetes Research Featured in Popular Science
What better way to describe the clinical trial experience than through the eyes of a study participant? In this month's Popular Science magazine, journalist Catherine Price writes about her experience in a new-onset type 1 diabetes clinical study involving the monoclonal antibody anti-CD3. Not only does Catherine's story, Rebooting the Body, chronicle the long history of this research led by UCSF's Jeffrey Bluestone, PhD and Yale's Kevan Herold, MD, she also discusses other recent advances in reprogramming the immune system and stopping insulin-producing beta cell destruction. Previously, the New York Times published one of Catherine's essays, Thinking About Diabetes With Every Bite. Additionally, Catherine is a featured speaker at this month's UCSF Pediatric Diabetes Symposium & Kids Kamp . You can read more of Catherine's writing on diabetes at A Sweet Life.
Sign Up Today for Pediatric and Adult Patient Programs
Our annual UCSF Pediatric Diabetes Symposium & Kids Kamp is just around the corner! This year's program is scheduled for Saturday, March 20, 2010, 9 a.m. – 3 p.m., at the UCSF Mission Bay Campus in San Francisco. Even though Kids Kamp is at its maximum capacity and no additional children will be enrolled, adults with type 1 diabetes and parents of children with type 1 diabetes are encouraged to attend this educational event. Please RSVP to Kathleen Fraser.
This year's UCSF Diabetes Teaching Center’s Adult Patient Symposium is scheduled for Saturday, June 5, 2010, 7:45 a.m. – 12:30 p.m., at Genentech Hall on the UCSF Mission Bay Campus in San Francisco. For more information, contact Marina Demetsky.
CLINICAL TRIALS
The Diabetes Center at UCSF is among the premier institutions for clinical trials of emerging therapies in diabetes. Numerous clinical trials in type 1 and 2 diabetes are now underway.
Interested in participating? A sample of our trials currently enrolling patients:
Type 1 Diabetes: Thymoglobulin Intervention Study Seeking volunteers, 12 to 35 years of age, within 100 days of diagnosis [ JDRF story link ]
Type 1 Diabetes: GAD Study Seeking volunteers, 3 to 15 years of age, within 3 months of diagnosis
Type 1 Diabetes: TrialNet Natural History Study [Antibody Screening] Seeking relatives of people with type 1 diabetes, 1 to 45 years of age
Type 1 Diabetes: Islet Transplantation with Belatacept Seeking volunteers 18 and older, with type 1 diabetes and weighing less than 175 lbs
Type 2 Diabetes: Paleolithic-Type Diets and Metabolic Control Seeking volunteers 18 years of age and older with type 2 diabetes
Bone Study for Postmenopausal Women With or Without Type 2 Diabetes Seeking volunteers between 50 and 75 years old
APS1 and Autoimmune Disease Seeking volunteers at least 6 years old and weighing over 40 pounds who have either autoimmune disease, have evidence of autoimmunity, have a family member with autoimmunity, or do not have autoimmune disease (healthy volunteer control)
Non-Diabetes: Alpha Lipoic Acid and Insulin Resistance Seeking volunteers 20 to 60 years of age
For more opportunities, visit the Clinical Trials section of our website, or contact Kathleen Fraser, our Clinical Trials Recruitment Coordinator.
Diabetes Center at UCSF
If you wish to receive more information about the UCSF Diabetes Center’s clinical and research programs, or would like to financially support one or more of these efforts, please contact Suzanne Ritchie at 415-476-6334. You may also visit our donation website and designate your gift to “The Diabetes Center."
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