Featured Research

from universities, journals, and other organizations

Decade of effort yields diabetes susceptibility gene

Date:
October 6, 2011
Source:
University of Wisconsin-Madison
Summary:
Ten years of meticulous mouse breeding, screening, and record-keeping have finally paid off for researchers who have identified a diabetes susceptibility gene.

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.


Story Source:

The above story is based on materials provided by University of Wisconsin-Madison. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sushant Bhatnagar, Angie T. Oler, Mary E. Rabaglia, Donald S. Stapleton, Kathryn L. Schueler, Nathan A. Truchan, Sara L. Worzella, Jonathan P. Stoehr, Susanne M. Clee, Brian S. Yandell, Mark P. Keller, Debbie C. Thurmond, Alan D. Attie. Positional Cloning of a Type 2 Diabetes Quantitative Trait Locus; Tomosyn-2, a Negative Regulator of Insulin Secretion. PLoS Genetics, 2011; 7 (10): e1002323 DOI: 10.1371/journal.pgen.1002323

Cite This Page:

University of Wisconsin-Madison. "Decade of effort yields diabetes susceptibility gene." ScienceDaily. ScienceDaily, 6 October 2011. <www.sciencedaily.com/releases/2011/10/111006173434.htm>.
University of Wisconsin-Madison. (2011, October 6). Decade of effort yields diabetes susceptibility gene. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2011/10/111006173434.htm
University of Wisconsin-Madison. "Decade of effort yields diabetes susceptibility gene." ScienceDaily. www.sciencedaily.com/releases/2011/10/111006173434.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Ebola Cases Could Reach 1.4 Million Within 4 Months

Ebola Cases Could Reach 1.4 Million Within 4 Months

Newsy (Sep. 23, 2014) Health officials warn that without further intervention, the number of Ebola cases in Liberia and Sierra Leone could reach 1.4 million by January. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Cases to Triple in Weeks Without Drastic Action

WHO: Ebola Cases to Triple in Weeks Without Drastic Action

AFP (Sep. 23, 2014) The number of Ebola infections will triple to 20,000 by November, soaring by thousands every week if efforts to stop the outbreak are not stepped up radically, the WHO warned in a study on Tuesday. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
5 Ways Men Can Prevent Most Heart Attacks

5 Ways Men Can Prevent Most Heart Attacks

Newsy (Sep. 23, 2014) No surprise here: A recent study says men can reduce their risk of heart attack by maintaining a healthy lifestyle, which includes daily exercise. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

More Coverage


Diabetes Susceptibility Gene Identified: Tomosyn-2 Regulates Insulin Secretion

Oct. 6, 2011 A group of researchers has pinpointed a gene that confers diabetes susceptibility in obese mice. This study also shows that its protein tomosyn-2 acts as a brake on insulin secretion from the ... read more

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins