Navigation Links
Penn study explains paradox of insulin resistance genetics

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
University of Pennsylvania School of Medicine

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:
Related Image:
Penn study explains paradox of insulin resistance genetics
(Date:11/25/2015)... , ... November 25, 2015 , ... ... has focused on providing comprehensive solutions involving adult stem cell therapies to patients ... officially deemed the “Regenestem” name as a Registered Trademark (RTM). , Organizations are ...
(Date:11/25/2015)... ... 25, 2015 , ... Bunion Bootie , the newest ... of the early holiday shopping season. Starting Wednesday November 25th, Bunion Booties are ... Friday promotional pricing is in addition to any automatic discounts applied when buying ...
(Date:11/24/2015)... ... November 24, 2015 , ... Eric C. Seidel, ... many benefits of the revolutionary BIOLASE WaterLase iPlus 2.0™ system. This advanced laser ... used by a dentist in Gettysburg, PA . From routine visits to ...
(Date:11/24/2015)... ... , ... New patients who wish to seek treatment for missing teeth can ... her Mississauga, ON practice. Dr. Williams has been providing dental service for over 34 ... Missing teeth can lead to a variety of complications if they are not replaced ...
(Date:11/24/2015)... ... ... Charitable giving is at its peak during the holidays. In fact, ... the year totalling over $358 billion in 2014. With more than 1.5 million ... individuals who want to “give back” during the holidays. , “With so many charities ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... 2015 Research and Markets ( ) ... - Global Forecast to 2020" report to their ... for 37.21% of the total market share in 2014. ... region is projected to growth at the highest CAGR ... primarily to the fast growing water, industrial gas treatment, ...
(Date:11/24/2015)... 25, 2015 WuXi PharmaTech (Cayman) Inc. ("WuXi" ... open-access R&D capability and technology platform company serving the ... China and the ... extraordinary general meeting of shareholders held today, the Company,s ... and approve the previously announced agreement and plan of ...
(Date:11/24/2015)... N.C. , Nov. 24, 2015  In the ... projects in an effort to quickly uncover new insights, ... --> --> However, ... a market research project and ensure that all rules ... and industry standards. Another major barrier to efficiently launching ...
Breaking Medicine Technology: