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.
Deepfakes, digital doubles, and the law: Jennifer Rothman on protecting identity in the AI era
The evolution of AI technology may require more robust copyright laws and guardrails that protect people’s control of their own identities, says the Penn Carey Law professor.
Bold ideas and innovation on display at the Fall Research Expo
On Sept. 15, hundreds of posters were presented throughout Houston Hall at the annual Fall Research Expo, representing the research projects of 410 undergraduate students conducted through the Center for Undergraduate Research.
Exposure to air pollution worsens Alzheimer’s disease
New research from Penn Medicine finds living in areas with high concentration of air pollution is associated with increased buildup of amyloid and tau proteins in the brains of Alzheimer’s patients, accelerating cognitive decline.
