New Study Explores Relationship Between Insulin and Fatty Liver, as Reported by DiabeticLive.com
The research team demonstrated that the major downstream path used by insulin to control the genes is also related to the pathways that control the metabolization of nutrients, as reported by DiabeticLive.com.
Orlando, FL (PRWEB) October 29, 2011
Lipid accumulation in the liver almost always accompanies insulin resistance and obesity, both warning signs of Type 2 diabetes. Such lipid accumulation can be deadly, leading to liver failure and hepatitis. However, doctors have been stumped as to why insulin-resistant livers also produce more fat.
Hormones, especially insulin, control the signals that tell the liver to produce fat. Morris Birnbaum, M.D., Ph.D., a professor of Medicine at the Perelman School of Medicine of the University of Pennsylvania, described the mechanism by which insulin alters the expression of genes that control lipid metabolism. Insulin normally promotes fat production in the liver, so a logical conclusion would be that an insulin-resistant liver would not produce fat. Insulin is normally responsible for turning off glucose output; for individuals who have insulin resistance, glucose output is too high, resulting in the high blood glucose levels that accompany diabetes. Treating the elevated blood sugar levels and the increased storage of fat associated with diabetes requires an understanding of the mechanisms that guide lipid metabolism.
Previous research has suggested that two proteinsÃ¢”transcription factors called FoxA2 and FoxO1Ã¢”are negatively regulated by, and act downstream of, an enzyme called kinase Akt/PKB, which is stimulated by insulin. Birnbaum has conducted previous studies which demonstrated that AkT/PKB is required for the accumulation of fat in the liver. Researchers have proposed that this relationship is one of the primary determinants of the fat content of the liver, which is often cited as a sign of increased lipids.
Dr. Birnbaum, who is also associate director of the Institute of Diabetes, Obesity, and Metabolism at the University of Pennsylvania, conducted a study which introduced mutations into certain genes; the findings demonstrated that permanently turning off the transcription factors could not be responsible for the protection from fat accumulation in the liver that the deletion of Atk2 provides.
The research team demonstrated that the major downstream path used by insulin to control the genes is also related to the pathways that control the metabolization of nutrients. They also showed that another arm of insulin signaling, one which likely has no relation to the nutrient pathway, also plays an important role in lipid metabolism, being responsible for increases in the production of lipid. The mTORC1 protein complex, another downstream target that is activated by Akt, plays a central role in the production of lipid by the body. The researchers hypothesized that these multiple pathways probably serve to ensure that the liver only produces fat in response to an increase in nutrients and a signal from insulin to increase lipid production.
Birnbaum stated that the discovery of new pathways can help scientists identify possible targets for treatment with medications.
“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,” said Birnbaum.
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For the original version on PRWeb visit: http://www.prweb.com/releases/prwebDiabetes/Fatty-Liver/prweb8920733.htm