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Projects 2006

Sponsoring Laboratory/Section:

Laboratory of Biological Modeling
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lab Chief:

Arthur Sherman, Ph.D.

Mentors:

Arthur Sherman, Ph.D.
Michael Quon

Contact Information:

e-mail: asherman@nih.gov
phone: (301) 496-4325

Laboratory Description:

We are involved in many projects related to diabetes, obesity, and hormone secretion.
See http://lbm.niddk.nih.gov and http://lbm.niddk.nih.gov/sherman for details.

Project Description:

One of the projects we have been involved in is modeling the signaling pathways of insulin action. Insulin promotes glucose uptake in muscle and both glucose uptake and fat storage in adipose cells. Although the reputation of insulin has been tarnished by the low-carb movement, it is actually essential for life. Resistance to the action of insulin is a common correlate of obesity and forces the body's insulin-secreting cells, the beta-cells of the pancreas, to work harder. When they fail to keep up with the increased demand, diabetes, a state of unregulated, mostly elevated, blood glucose levels ensues. Therefore, a better understanding of insulin action is important for making progress in preventing and treating diabetes.

We have previously published a model for insulin action (Quon et al, Am. J. Physiol. (Endocrinol. Metab.), 283:E1084-E1101, 2002). The proposed project is to extend this model to incorporate new data on the signaling pathways. We are particularly interested in exploring how positive feedback can enhance the reliability of the network response. This has been discussed for simple, idealized models in Brandman et al, Science, 310(5747):449-51, October 21, 2005), but we would like to investigate the concept in a detailed, realistic model for an important signaling pathway.