News & Research
Accili, Domenico , MD
Transcriptional regulation in diabetes
Focus: Insulin Action Insulin Resistance, Islet Biology, Signal Transduction (Non-Insulin Action)-Transgenic Models
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2007
Project End Date: June 30, 2011
Research Description
We study the pathogenesis of insulin resistance and beta cell failure in type 2 diabetes. This laboratory utilizes genetically modified mice to analyze the complex genetics of type 2 diabetes. These studies focus on three different areas: (1), interactions among different tissues in the pathogenesis of insulin resistance; (2), role of forkhead transcription factors in insulin action; and (3), role of insulin and insulin-like growth factors in pancreatic development and beta cell function. Our work has shown that the Foxo sub-family of transcription factors plays a key role in insulin action in liver, beta cells, hypothalamus, muscle and adipose tissue. Foxo1 increases glucose production and triglyceride synthesis in liver and is inhibited by insulin via translocation from the cell nucleus to the cytoplasm.
Reseacher Profile
Mentor: Domenico Accili, MD Fellow: Michihiro Matsumoto
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes? The studies supported by the American Diabetes Association in the PI's laboratory focus on the role of the liver in glucose production and lipoprotein turnover. Current work is focused on mechanisms linking insulin action and ApoB secretion in liver, a key aspect of diabetic dyslipidemia leading to atherosclerosis and heart disease. Insulin resistance, by causing an increase in nuclear Foxo1, promotes glucose production and triglyceride synthesis, two abnormalities that are commonly found in diabetics and can potentially explain both hyperglycemia and the increase in cardiovascular disease and atherosclerosis seen in diabetics. Thus, studies supported by this Award will allow the Accili laboratory to make progress in understanding one the critical issues in diabetes pathogenesis and care.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond? We are trying to understand the mechanism by which glucose and fat production in the liver of diabetic patients is increased. This abnormality is the main cause of diabetic complications and of the worsening of diabetes control over time. By understanding why the diabetic liver produces excess glucose and fat, we are more likely to find a cure that is effective at combating both hyperglycemia and dyslipidemia (high "bad" cholesterol and triglycerides).
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts? It's an important disease, and not nearly enough is being done to combat it. It's fascinating science and provides an opportunity to work for the greater common good.
In what direction do you see the future of diabetes research going? More emphasis on mechanisms of complications, early intervention and discovery of alternative pathways of insulin sensitivity.
