Featured Research

from universities, journals, and other organizations

Study explains paradox of insulin resistance genetics

Date:
October 26, 2011
Source:
University of Pennsylvania School of Medicine
Summary:
A paradox in understanding insulin resistance is figuring out why insulin-resistant livers make more fat. Insulin resistance occurs when the body does a poor job of lowering blood sugars. The signals to make lipid after a meal come from hormones -- most notably insulin -- and the direct effect of nutrients on the liver. Researchers describe the pathway that insulin uses to change the levels of gene expression that control lipid metabolism.

Sections of liver from an obese mouse at increasing magnifications (left panels). Red is the lipid in the cell in the form of stained droplets. Sections of liver from an obese mouse lacking Akt (right panels), which blocks the massive accumulation of fat, mimicking the appearance of a normal liver. Blue are liver cell nuclei and the white is space between cells, such as blood vessels, and ducts.
Credit: Rachael Easton, Perelman School of Medicine, University of Pennsylvania

Obesity and insulin resistance are almost inevitably associated with increases in lipid accumulation in the liver, a serious disease that can deteriorate to hepatitis and liver failure. A real paradox in understanding insulin resistance is figuring out why insulin-resistant livers make more fat. Insulin resistance occurs when the body does a poor job of lowering blood sugars.

The signals to make lipid after a meal come from hormones -- most notably insulin -- and the direct effect of nutrients on the liver. In a recent issue of Cell Metabolism, Morris Birnbaum, MD, PhD, professor of Medicine at the Perelman School of Medicine, University of Pennsylvania, describes the pathway that insulin uses to change the levels of gene expression that control lipid metabolism. Birnbaum is also associate director of the Institute of Diabetes, Obesity, and Metabolism at Penn.

Since insulin normally stimulates fat synthesis in the liver, the expectation is that an insulin-resistant liver would not be able to make lipid. Insulin normally shuts off glucose output and during insulin resistance output is too high. This contributes to the high blood sugar of diabetes. In order to treat the lipid accumulation as well as the glucose abnormalities in type 2 diabetes, it is important to understand the pathways that regulate lipid metabolism.

Researchers have suggested that two transcription factors, proteins called FoxA2 and FoxO1, act downstream of, and are negatively regulated by, an enzyme stimulated by insulin called kinase Akt/PKB. Birnbaum had previously shown that this kinase is required for lipid accumulation in the liver. This system is proposed by researchers as a key determinant of liver triglyceride content, one indicator of increased lipids.

In the current study, the team used a technique of introducing mutations into specific genes to show that having these transcriptions factors turned on all the time cannot account for the protection from lipid accumulation in the liver afforded by deleting Akt2 in the liver.

The researchers showed that the major downstream path that insulin uses to regulate these genes converges with the pathways that the body uses to metabolize nutrients. In addition, another arm of insulin signaling (which is probably independent of the nutrient pathway) is also required for the increase in lipid metabolism. Another downstream target turned on by Akt, the mTORC1 protein complex, is required for the body to make lipid. Having multiple pathways is probably a way that the liver makes sure that lipid synthesis is activated only when there is an increase in nutrients and there is a signal from insulin, surmise the researchers.

"Since a therapeutic goal is to prevent this lipid accumulation, any time we identify a novel pathway it raises the hope that there is a previously unknown target out there for a new type of drug," concludes Birnbaum.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Min Wan, KarlaF. Leavens, Danish Saleh, RachaelM. Easton, DavidA. Guertin, TimothyR. Peterson, KlausH. Kaestner, DavidM. Sabatini, MorrisJ. Birnbaum. Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 Independent of the Transcription Factors FoxA2, FoxO1, and SREBP1c. Cell Metabolism, 2011; 14 (4): 516 DOI: 10.1016/j.cmet.2011.09.001

Cite This Page:

University of Pennsylvania School of Medicine. "Study explains paradox of insulin resistance genetics." ScienceDaily. ScienceDaily, 26 October 2011. <www.sciencedaily.com/releases/2011/10/111025122613.htm>.
University of Pennsylvania School of Medicine. (2011, October 26). Study explains paradox of insulin resistance genetics. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2011/10/111025122613.htm
University of Pennsylvania School of Medicine. "Study explains paradox of insulin resistance genetics." ScienceDaily. www.sciencedaily.com/releases/2011/10/111025122613.htm (accessed October 2, 2014).

Share This



More Health & Medicine News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
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