Arthur Sherman, National Institute of Diabetes and Digestive and Kidney Diseases, will receive the Arthur T. Winfree Prize for his work on biophysical
mechanisms underlying insulin secretion from pancreatic beta-cells. Since
insulin plays a key role in maintaining blood glucose, this is of basic physiological
interest and is also important for understanding the causes and treatment of type 2 diabetes, which arises from a combination of defects in insulin secretion and
insulin action. The Arthur T. Winfree Prize was established in memory of Arthur T. Winfree’s contributions to mathematical biology. This prize is to honor a
theoretician whose research has inspired significant new biology. The Winfree
Prize consists of a cash prize of $500 and a certificate given to the recipient. The
winner is expected to give a talk at the Annual Meeting of the Society for Mathematical Biology (Montreal 2019).
Read how Sherman explains his research in lay language on a NIDDK website.
Insulin is a hormone that allows the body to use carbohydrates for quick energy. This spares fat for long-term energy storage and protein for building muscle and regulating cellular processes. Without sufficient insulin many tissues, such as muscle, cannot use glucose, the product of digestion of carbohydrates, as a fuel. This leads to diabetes, a rise in blood sugar that damages organs. It also leads to heart disease, kidney failure, blindness, and finally, premature death. We use mathematics to study how the beta cells of the pancreas know how much glucose is available and how much insulin to secrete, as well as how failure of various components of insulin secretion contributes to the development of diabetes.
When I was at NIH, Sherman worked with John Rinzel studying bursting. Here’s a page from my research notebook, showing my notes from a talk that Artie (as we called him then) gave thirty years ago. A sketch of a bursting pancreatic beta cell is in the bottom right corner.
I will trace the history of models for bursting, concentrating on square-wave bursters descended from the Chay-Keizer model for pancreatic beta cells. The model was originally developed on a biophysical and intutive basis but was put into a mathematical context by John Rinzel's fast-slow analysis. Rinzel also began the process of classifying bursting oscillations based on the bifurcations undergone by the fast subsystem, which led to important mathematical generalization by others. Further mathematical work, notably by Terman, Mosekilde and others, focused rather on bifurcations of the full bursting system, which showed a fundamental role for chaos in mediating transitions between bursting and spiking and between bursts with different numbers of spikes. The development of mathematical theory was in turn both a blessing and a curse for those interested in modeling the biological phenomena—having a template of what to expect made it easy to construct a plethora of models that were superficially different but mathematically redundant. This may also have steered modelers away from alternative ways of achieving bursting, but instructive examples exist in which unbiased adherence to the data led to discovery of new bursting patterns. Some of these had been anticipated by the general theory but not previously instantiated by Hodgkin-Huxley-based examples. A final level of generalization has been the addition of multiple slow variables. While often mathematically reducible to models with a one-variable slow subsystem, such models also exhibit novel resetting properties and enhanced dynamic range. Analysis of the dynamics of such models remains a current challenge for mathematicians.
Congratulations to Arthur Sherman, for this well-deserved honor.
Arthur Sherman giving a talk at the Colorado School of Mines, October 2017.
I am an emeritus professor of physics at Oakland University, and coauthor of the textbook Intermediate Physics for Medicine and Biology. The purpose of this blog is specifically to support and promote my textbook, and in general to illustrate applications of physics to medicine and biology.
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