Navigation Links
Penn study explains paradox of insulin resistance genetics
Date:10/25/2011

PHILADELPHIA - 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.


'/>"/>
Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Wayne State University study of heroin users to examine links between stress, drug use
2. Study Casts Doubt on Hot Dogs Link to Colon Cancer
3. Study: Obesity limits effectiveness of flu vaccines
4. Soft Drinks Linked to Violent Tendencies in Teens: Study
5. Yoga, Stretching Classes Outdo Self-Care for Back Pain: Study
6. Experimental Vaccine Shows Promise for Lung Cancer: Study
7. Study confirms males and females have at least 1 thing in common: Upregulating X
8. Breast Reconstruction Boosts Womens Emotional Well-Being: Study
9. Hockey Fistfights Rarely Cause Injuries, Study Claims
10. Mayo Clinic study: PSA test valuable in predicting biopsy need, low-risk prostate cancer
11. Study finds no correlation between primary kidney stone treatment and diabetes
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Penn study explains paradox of insulin resistance genetics
(Date:9/22/2017)... ... September 22, 2017 , ... The freshly released app Smart ... to Smart Mart, customers can now order vegetable, fruit, snacks, dairy, or any ... find clothing at discounted prices. Apart from this, Smart Mart has emphasized upon ...
(Date:9/22/2017)... Greenwich, Connecticut (PRWEB) , ... September 22, 2017 ... ... to conquering Lyme and other tick-borne diseases through research, education and awareness, today ... , A noted immunologist and microbiologist, Dr. Sellati has more than 20 ...
(Date:9/21/2017)... ... 2017 , ... 38-Year-Old Plastic Surgeon Gill at Aesthetic Surgery Center is Saluted ... announce that Plastic Surgeon Kiranjeet Gill has been awarded as one of the 15th ... award that was started in 2003 to salute young achievers in Southwest Florida who ...
(Date:9/21/2017)... ... September 21, 2017 , ... SABRE is raising awareness ... September 11 to the end of November. , The Chicago, Illinois, based self-defense brand ... and teach them about the ease of taking their personal safety into their own ...
(Date:9/21/2017)... ... September 21, 2017 , ... ... Management Report**, http://www.fdanews.com/products/54818-promotional-communication      , In the competitive world of drug and ... while staying in compliance with FDA rules. , The FDA has issued two ...
Breaking Medicine News(10 mins):
(Date:9/9/2017)... 8, 2017 ... Unit coming to Washington DC ... When: Tuesday, September 12 th – Monday, September 18 th .The ... free MRI brain scans to the public.Where:  BTF,s ... at 501 K Street NW, Washington, D.C.What:BTF brings its nationwide initiative, the ...
(Date:9/9/2017)... Sept. 9, 2017  Eli Lilly and Company (NYSE: ... secondary endpoint data for lasmiditan, an investigational, oral, first-in-class ... statistically significant improvements compared to placebo in the Phase ... at the 18th Congress of the International Headache Society ... "The data presented today demonstrate lasmiditan,s potential to reduce ...
(Date:9/7/2017)... RANCHO MIRAGE, Calif. , Sept. 7, 2017  For nearly two ... and service in the Assisted Reproduction Insurance industry. Today, New Life Agency ... expensive fertility medications. ... http://pharmacarecard.com/ (PRNewsfoto/PharmaCareCard) ... ...
Breaking Medicine Technology: