Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Decade of Effort Yields Diabetes Susceptibility Gene

10.10.2011
Ten years of meticulous mouse breeding, screening, and record-keeping have finally paid off for Alan Attie and his lab members.

The University of Wisconsin–Madison researchers’ efforts, published Oct. 6 in the journal PLoS Genetics, pinpointed a gene that confers diabetes susceptibility in obese mice.

They also showed that the protein coded by the gene, called tomosyn-2, acts as a brake on insulin secretion from the pancreas.

“It’s too early for us to know how relevant this gene will be to human diabetes,” says Attie, a UW–Madison biochemistry professor, “but the concept of negative regulation is one of the most interesting things to come out of this study and that very likely applies to humans.”

In a properly tuned system, insulin secreted into the blood after eating helps maintain blood sugar at a safe level. Too little insulin (as in type 1 diabetes) or insulin resistance (as in type 2 diabetes) leads to high blood sugar and diabetic symptoms. Too much insulin can drive blood glucose dangerously low and lead to coma or even death in a matter of minutes.

“You can imagine that if you’re in a fasted state, you don’t want to increase your insulin, so it’s very important to have a brake on insulin secretion,” says Angie Oler, one of the lead authors. “It needs to be stopped when you’re not eating and it needs to start again when you do eat.”

The group honed in on tomosyn-2 while searching for genes that contribute to diabetes susceptibility in obese animals.

Why study fat mice?

“It takes more insulin to achieve the same glucose-lowering effect in an obese person than it does in a lean person. If you can produce that extra insulin – and most people do – you’ll be okay. You will avoid diabetes at the expense of having to produce and maintain a higher insulin level,” Attie explains. “Most of the type 2 diabetes that occurs in humans today would not exist were it not for the obesity epidemic.”

But an insufficient insulin response leads to diabetes, and the same is true in mice.

Painstaking genetic analyses and comparisons of obese diabetes-resistant and diabetes-susceptible mouse strains ultimately revealed a single amino acid difference that destabilizes the tomosyn-2 protein in the diabetes-resistant mice, effectively releasing the brake on insulin secretion and allowing those animals to release enough insulin to avoid diabetes.

The researchers also confirmed that the human form of tomosyn-2 inhibits insulin secretion from human pancreatic beta cells.

Though diabetes is highly unlikely to be caused by a single gene, identifying important biological pathways can suggest clinically useful targets. “This study shows the power of genetics to discover new mechanisms for a complex disease like type 2 diabetes,” says postdoctoral fellow Sushant Bhatnagar, a co-lead author of the paper.

“Now we know there are proteins that are negative regulators of insulin secretion. Very likely they do the same thing in human beta cells, and it motivates us to move forward to try to figure out the mechanisms behind that negative regulation,” Attie says.

The American Diabetes Association and the National Institutes of Health provided research funding.

Jill Sakai, jasakai@wisc.edu, (608) 262-9772
Alan Attie, adattie@wisc.edu, (608) 262-1372

Jill Sakai | Newswise Science News
Further information:
http://www.wisc.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

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”...

Im Focus: Dresdner scientists print tomorrow’s world

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...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>