Featured Research

from universities, journals, and other organizations

Insulin Resistance And Obesity Avoided In Genetically Modified Mice, As Reported In Science

Date:
March 5, 1999
Source:
American Association For The Advancement Of Science
Summary:
A team of Canadian scientists has identified a potentially useful target for drugs to treat type II diabetes and obesity. In the scientists' experiments, genetically engineered mice lacking a specific enzyme were able to resist weight gain and to avoid the decreased sensitivity to insulin that characterizes type II diabetes, even when fed an extremely high calorie, high fat diet.

Washington D.C. - A team of Canadian scientists has identified a potentially useful target for drugs to treat type II diabetes and obesity. In the scientists' experiments, genetically engineered mice lacking a specific enzyme were able to resist weight gain and to avoid the decreased sensitivity to insulin that characterizes type II diabetes, even when fed an extremely high calorie, high fat diet. The results are reported in the 5 March issue of Science.

The finding raises hopes that researchers might someday design a drug for humans that mimics these effects by targeting the same enzyme. "It will certainly take some time to find a compound useful for humans based on our mouse model, but it has the possibility of being a really significant drug if it works," said Brian Kennedy of the Merck Frosst Center for Therapeutic Research in Pointe Claire-Dorval, Quebec, Canada, who was a member of the research team.

In 1995, there were 35 million cases of type II diabetes, or "non-insulin-dependent diabetes," worldwide, according to the World Health Organization, which predicts that the number will radically increase over the next 25 years. Type II diabetes usually develops gradually in people over 40, and overweight people are at particularly high risk for the disease. Diabetes occurs when the body's cells are unable to absorb enough blood sugar, or glucose, into their cells. This lack of cellular "fuel" and the high levels of glucose in the blood stream cause weight loss, fatigue, and a variety of long-term complications.

To store and use glucose, cells need assistance from the hormone insulin, which controls a complex series of steps to remove glucose from the bloodstream and sequester it in the cells. This set of steps is called the insulin "signal." People with type I diabetes (the more severe and early-onset form of the disease) do not produce insulin at all and must give themselves regular insulin injections. People with type II diabetes do produce insulin but their bodies are resistant to its effects.

Previous research has suggested that an enzyme known as PTP-1B might somehow play a role in reducing insulin's ability to regulate blood sugar levels. To investigate this possibility, Mounib Elchebly of McGill University and his colleagues "knocked out" the mouse gene responsible for the production of this enzyme. Compared to normal mice, the mice lacking the enzyme had significantly lower amounts of glucose in their blood after eating and even lower amounts of insulin. Thus, deleting the PTP-1B enzyme appeared to increase the mice's sensitivity to insulin: they were able to use smaller amounts of the hormone to efficiently move glucose from the bloodstream into the cells.

To further probe the insulin signaling process, the scientists fed both normal and knockout mice a diet extremely high in calories, 50 percent of which were from fat. As expected, normal mice quickly gained extra weight and developed obesity-related insulin resistance. In contrast, the knockout mice did not gain much weight and had normal insulin and glucose levels.

The exact task that the PTP-1B enzyme performs in sending off the insulin signal has not been pinned down yet, but some of Elchebly and colleagues' results suggest a likely possibility. It appears that the enzyme deactivates the cell's insulin receptor. (Receptors are "docking points" on the cell's surface for molecules that interact with the cell.) "We knew how the receptor is turned on, but not how it might be turned off. PTP-1B could be one way to do that," Kennedy said.

With no interference from the enzyme, the insulin receptors of the knockout mice seemed to remain active longer than the receptors of normal mice. This larger window of opportunity for insulin signaling could render PTP-1B-deficient mice more sensitive to the effects of the hormone.

PTP-1B also appears to play a role in regulating metabolism, as evidenced by the fact that the knockout mice resisted gaining weight more successfully than the normal mice. However, more work must be done to understand how this occurs.


Story Source:

The above story is based on materials provided by American Association For The Advancement Of Science. Note: Materials may be edited for content and length.


Cite This Page:

American Association For The Advancement Of Science. "Insulin Resistance And Obesity Avoided In Genetically Modified Mice, As Reported In Science." ScienceDaily. ScienceDaily, 5 March 1999. <www.sciencedaily.com/releases/1999/03/990305073924.htm>.
American Association For The Advancement Of Science. (1999, March 5). Insulin Resistance And Obesity Avoided In Genetically Modified Mice, As Reported In Science. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/1999/03/990305073924.htm
American Association For The Advancement Of Science. "Insulin Resistance And Obesity Avoided In Genetically Modified Mice, As Reported In Science." ScienceDaily. www.sciencedaily.com/releases/1999/03/990305073924.htm (accessed September 18, 2014).

Share This



More Health & Medicine News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. Video provided by Reuters
Powered by NewsLook.com
What HealthKit Bug Means For Your iOS Fitness Apps

What HealthKit Bug Means For Your iOS Fitness Apps

Newsy (Sep. 18, 2014) Apple has delayed the launch of the HealthKit app platform, citing a bug. Video provided by Newsy
Powered by NewsLook.com
Residents Vaccinated as Haiti Fights Cholera Epidemic

Residents Vaccinated as Haiti Fights Cholera Epidemic

AFP (Sep. 18, 2014) Haitians receive the second dose of the vaccine against cholera as part of the UN's vaccination campaign. Duration: 00:34 Video provided by AFP
Powered by NewsLook.com
Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
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:
from the past week

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