ACMD Seminar: Modeling the Pathogenesis and Treatment of Diabetes

Dr. Arthur Sherman
Chief, Laboratory of Biological Modeling
National Institutes of Health

Tuesday, July 17, 15:00 - 16:00
Building 101, Lecture Room C
Gaithersburg

Tuesday, July 17, 13:00 - 14:00
Building 1, Room 4072
Boulder

Host: Michael Mascagni

Abstract: We have developed a mathematical model for the pathogenesis of type 2 diabetes centered on the negative feedback provided by enhanced beta-cell function and mass in response to insulin resistance.  The model describes disease onset and remission as crossing a threshold separating bistable states of health and disease, which may account for the success of bariatric surgery to reverse diabetes once it is established and the failure of typical diet and exercise to do so.  The model therefore places high priority on early detection and prevention.  We have shown mathematically and clinically that more information on risk can be obtained by using all time points during oral glucose tolerance tests than by using the standard baseline and two-hour points.  We have also generated new hypotheses for the differential patterns of risk and progression in populations of East Asian and African origin compared to Europeans.

Bio: Dr. Sherman was trained as an applied mathematician with interests in scientific computing and mathematical biology at New York University under Charles Peskin.  In 1986, he joined the Mathematical Research Branch (MRB), NIDDK, as a post-doctoral fellow with John Rinzel.  His work centered on using differential equations to model the calcium and electrical activity that underlie pulsatile insulin secretion from pancreatic beta cells, with parallel work on electrical activity in neurons and pituitary cells and on neurotransmitter release.  He was promoted to tenure track in 1989 and was tenured in 1996.  In 2005 he became chief of the MRB, which was renamed the Laboratory of Biological Modeling (LBM).  Today LBM hosts four principal investigators whose work covers a range of focus areas related to diabetes, including obesity and metabolism, as well as other efforts that can be broadly characterized as systems biology.  Recently Dr. Sherman's work on the normal functioning of beta cells has turned toward modeling the role of beta-cell failure combined with insulin resistance in the pathogenesis of type 2 diabetes.