Navigation Links
Early trigger for type-1 diabetes found in mice, Stanford scientists report
Date:8/26/2008

STANFORD, Calif. - Scientists at the Stanford University School of Medicine are shedding light on how type-1 diabetes begins.

Doctors have known the disease is caused by an autoimmune attack on the pancreas, but the exact trigger of the attack has been unclear. Now, a new study in mice implicates the immune signal interferon-alpha as an early culprit in a chain of events that upend sugar metabolism and make patients dependent on lifelong insulin injections.

"We never considered that interferon-alpha could be a major player in early type-1 diabetes," said Qing Li, MD, PhD, a postdoctoral scholar in microbiology and immunology who was the primary author of a paper describing the new result. The study is published in today's issue of Proceedings of the National Academy of Sciences. "This was a pretty surprising finding."

Interferon-alpha normally helps the body fight viruses. Synthetic interferon-alpha is injected as a drug for treating hepatitis C and some forms of cancer, Li noted.

"Everybody's been wondering what process initiates type-1 diabetes," said Hugh McDevitt, MD, professor of microbiology and immunology and the study's senior author.

Type-1 diabetes is caused by complete deficiency of insulin, a hormone that helps the body store and burn sugar. About 1 million Americans have the disease, also known as juvenile diabetes because it tends to be diagnosed in children and young adults, for which there is no effective prevention or cure. Diabetes is a leading cause of heart disease, blindness, limb amputations and kidney failure.

The early pathology of type-1 diabetes is hard to study in humans, McDevitt said, because it's almost impossible to predict who will get the disease and when it will develop. Scientists have relied on animal models, such as diabetic mice, because they predictably develop high blood sugar and other features of the human disease.

To pinpoint interferon-alpha, Li and McDevitt worked backwards from what they knew about how type-1 diabetes starts. Prior studies in diabetic mice showed a pathogenic role for immune cells called CD4+ T cells. These cells are an early player in the immune attack on the body's insulin factories, pancreatic beta cells. The scientists used silicon gene-chip technology to measure which genes are revved up in the CD4+ T cells just before they assault the pancreas. The measurements fell into a pattern: many of the upregulated genes were known to be controlled by interferon-alpha.

To confirm the signal's nefarious role, the researchers gave mice an antibody that blocks interferon-alpha activity several weeks before the animals were expected to develop diabetes. Thwarting interferon-alpha delayed the start of the disease by an average of four weeks, and, in 60 percent of treated mice, it prevented diabetes entirely.

The finding confirmed the importance of interferon-alpha and helped the scientists connect the dots between normal mouse physiology and early diabetes. Mice are born with more pancreatic beta cells than they need, Li noted. The extras soon undergo programmed cell death, leaving plenty of working beta cells to pump out insulin. However, in mice that develop diabetes, debris left behind by the dying cells triggers an inappropriate immune response, with lots of interferon-alpha. The interferon-alpha cues immune destruction of more and more beta cells, causing insulin deficiency and diabetes.

The mechanism may be more complex in humans, the scientists cautioned, explaining that while their new finding goes a long way toward explaining the beginnings of diabetes in the mice, additional genetic and environmental factors influence the human disease. But the basic principle of disease is likely the same in diabetic mice and humans, they said.

"A normal process - programmed cell death - causes a normal response," McDevitt said. "But it does this in such a way that, in a small subset of the population, it starts them on the road to type-1 diabetes."


'/>"/>

Contact: Erin Digitale
digitale@stanford.edu
650-724-9175
Stanford University Medical Center
Source:Eurekalert

Related medicine news :

1. Pot bellies linked to early signs of cardiovascular disease
2. Eye-staining technique offers early detection for dry eye syndrome
3. Early Weight Loss in Women Linked to Dementia
4. Isolation of a new gene family essential for early development
5. U of M study: Early treatment can reverse heart damage
6. Gerresheimer to be Included in the SDAX Early Decision on Inclusion in the MDAX on September 5, 2007
7. Rock N Roll: Sex, Drugs and an Early Exit
8. Pop stars more than twice as likely to die an early death
9. Exercise and yoga improves quality of life in women with early-stage breast cancer
10. Research says doctors gender may hinder early diagnosis of heart disease in women
11. Antidepressant shows early promise in treating agitation and psychotic symptoms of dementia
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/21/2017)... ... July 21, 2017 , ... The Karen Miller ... to communities in the greater Birmingham area, is joining the Chris Hammond Youth ... people in the region. , The Chris Hammond Youth Foundation maintains athletic facilities ...
(Date:7/21/2017)... ... ... Fresh Wave® IAQ today announced the launch of its innovative Smoke ... the APPA 2017 Annual Conference and Exhibition in Booth #414. , Specifically ... use of harsh chemicals, Fresh Wave IAQ Smoke Away Air & Fabric Liquid is ...
(Date:7/21/2017)... , ... July 21, 2017 , ... Hospital M&A activity ... HealthCareMandA.com . The number of hospital acquisitions rose to 23 in the second quarter, ... and up 15% from the 20 announced deals in the year-ago second quarter. Only ...
(Date:7/21/2017)... ... ... The Margarian Law Firm has filed a class action lawsuit against ... no ginger. Dr. Pepper produces the “Canada Dry” brand of ginger ale products. In ... Ginger Ale claims on its bottle that it is made from real ginger. , ...
(Date:7/21/2017)... Basking Ridge, NJ (PRWEB) , ... July 21, ... ... Hills (VNA) has received a $5,000 grant from the C. R. ... Adult Day Center at Somerset Hills , a service available through the ...
Breaking Medicine News(10 mins):
(Date:7/19/2017)... RALEIGH, N.C. , July 19, 2017  Mako ... Veteran Affairs, and the Military Family Assistance Fund (MFA) ... Louisiana to visit with their families one ... the funding to coordinate the travel and logistics needed ... supporting our deployed soldiers and their families. We just ...
(Date:7/14/2017)... 13, 2017 It should come as no surprise ... is in the midst of a crippling opioid epidemic. According ... the number of overdose deaths from opiate-based medications has quadrupled, ... a million dead from 2001 to 2015". During this time, ... has similarly quadrupled, drawing a compelling link between prescription and ...
(Date:7/12/2017)... CarpalAID is a revolutionary new product that relieves painful carpal tunnel ... syndrome affects more than 8 million people a year. Women suffer ... common methods of treating CTS are painful surgery, the use of ... ... is a clear patch worn on the palm of the hand. ...
Breaking Medicine Technology: