Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Early trigger for type 1 diabetes found in mice

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."

Erin Digitale | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>