Featured Research

from universities, journals, and other organizations

Researchers Find Potential Mechanism Linking Obesity To Type 2 Diabetes

Date:
June 18, 2001
Source:
Beth Israel Deaconess Medical Center
Summary:
Problems with a protein buried deep within pancreatic beta cells may explain how obesity evolves into type 2 diabetes, according to new evidence from researchers at Beth Israel Deaconess Medical Center and their colleagues.

BOSTON -- Problems with a protein buried deep within pancreatic beta cells may explain how obesity evolves into type 2 diabetes, according to new evidence from researchers at Beth Israel Deaconess Medical Center and their colleagues.

Related Articles


The experiments in mice suggest a potential new approach to therapies in humans. The study is published in the June 15 issue of the journal Cell.

“The ultimate question is to understand if the mechanism that works in mice also operates in humans,” says senior author Brad Lowell, M.D., Ph.D., an endocrinology researcher at Beth Israel Deaconess. “We’ve done the kind of research we call proof of principle. It will stimulate new research to find out how broadly the mechanism operates and if it accounts for beta cell dysfunction in type 2 diabetes in humans.”

Diabetes is one of the leading causes of death and disability in this country, affecting an estimated 16 million Americans, about one-third of whom don’t know they have the disease. Type 2 diabetes accounts for about 90 percent of diabetes cases, and it is clear that obesity promotes the development of type 2 diabetes.

Normally, a meal triggers the pancreas to release the hormone insulin, which prompts muscle and fat cells to take in necessary glucose from the blood. Insulin also turns off glucose production by the liver. In the process leading up to type 2 diabetes, the body’s cells somehow become less responsive to insulin, known as insulin resistance. Glucose builds up in the blood, which triggers the pancreas to produce more insulin. For months or years, the number of insulin-producing pancreatic cells increase, and each pancreatic beta cell also produces more insulin, temporarily overriding the resistance. Eventually, the pancreas exhausts its ability to make enough insulin to compensate for the resistance, causing the chronic high blood sugar and symptoms of diabetes.

The new study suggests that a protein known as uncoupling protein-2, or UCP2, may play a pivotal role in the transition from insulin resistance to diabetes. Normally, glucose generates a signal within pancreatic beta cells, which triggers them to secrete insulin. UCP2 interferes with the glucose signal inside beta cells, which limits insulin secretion, according to a series of studies in mouse models lead by Beth Israel Deaconess researcher Chen-Yu Zhang, M.D., Ph.D., also an instructor in medicine at Harvard Medical School.

"If they have UCP2, the mice secrete less insulin at any given level of blood glucose,” says Lowell who is also an associate professor of medicine at Harvard Medical School. “If they don’t have UCP2, the mice secrete more insulin.”

Several lines of evidence suggest that UCP2 is a key component of glucose sensing by beta cells, and that the protein links obesity, beta cell dysfunction and type 2 diabetes. In one experiment, mice genetically engineered to lack the UCP2 gene released more insulin in response to the same amounts of glucose compared to normal mice, showing UCP2 works by reducing insulin secretion in response to blood glucose levels. Another mouse model of obesity-induced diabetes showed high levels of protein in their beta cells, leading to the hypothesis that increased UCP2 in obesity promotes the development of diabetes by impairing insulin secretion. Finally, when the researchers genetically engineered these obese, diabetic mice to lack UCP2, their insulin secretion was improved and their blood sugar levels were greatly reduced.

“The suggestion that pancreatic beta cell UCP2 is a useful target for the therapy of type 2 diabetes is exciting,” write Kenneth Polonsky and Clay Semenkovich, Washington University School of Medicine, St. Louis, in an accompanying review article in the same issue of Cell. “Additional studies are needed to confirm the hypothesis that an increase in UCP2 expression is an important trigger in the failure of beta cell compensation for insulin resistance, a poorly understood event that is critical to the development of type 2 diabetes.”

The researchers were supported by the National Institutes of Health, Eli Lilly, the Canadian Diabetes Association and the Human Frontier Science Program.

Co-authors on the paper include postdoctoral fellow Gyorgy Baffy, postdoctoral fellow Stefan Krauss, postdoctoral fellow Odile Peroni, postdoctoral fellow Danica Grujic, postdoctoral fellow Thilo Hagen, postdoctoral fellow Antonio Vidal-Puig, postdoctoral fellow Olivier Boss, HMS instructor Young-Bum Kim, and HMS assistant professor Xin Xiao Zheng, all researchers at Beth Israel Deaconess; postdoctoral fellow Pascale Perret and Howard Hughes Medical Investigator Gerald Shulman at Yale University School of Medicine; researcher Michael Wheeler, University of Toronto; and researcher Catherine Chan, University of Prince Edward Island.

Beth Israel Deaconess Medical Center is a major patient care, research and teaching affiliate of Harvard Medical School and a founding member of CareGroup Healthcare System. Beth Israel Deaconess is the third largest recipient of National Institutes of Health research funding among independent U.S. teaching hospitals.


Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Beth Israel Deaconess Medical Center. "Researchers Find Potential Mechanism Linking Obesity To Type 2 Diabetes." ScienceDaily. ScienceDaily, 18 June 2001. <www.sciencedaily.com/releases/2001/06/010615071657.htm>.
Beth Israel Deaconess Medical Center. (2001, June 18). Researchers Find Potential Mechanism Linking Obesity To Type 2 Diabetes. ScienceDaily. Retrieved November 29, 2014 from www.sciencedaily.com/releases/2001/06/010615071657.htm
Beth Israel Deaconess Medical Center. "Researchers Find Potential Mechanism Linking Obesity To Type 2 Diabetes." ScienceDaily. www.sciencedaily.com/releases/2001/06/010615071657.htm (accessed November 29, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
WHO Says Male Ebola Survivors Should Abstain From Sex

WHO Says Male Ebola Survivors Should Abstain From Sex

Newsy (Nov. 28, 2014) — WHO cites four studies that say Ebola can still be detected in semen up to 82 days after the onset of symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
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:

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