Phantom Bursting Models and Complex Bursting Patterns in Pancreatic Islets

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Bertram The investigator and his colleagues study the behavior ofinsulin-secreting pancreatic beta-cells. These cells display awide range of complex dynamics that are best understood with theaid of mathematical modeling and analysis. The investigator hasrecently developed a new mathematical model for beta-cells thatpostulates an intracellular calcium subspace compartment locatedbetween the endoplasmic reticulum and the cell membrane. Thismodel is based on recent data from a collaborating lab, and isbeing further developed as new experiments are performed. Onedirection of development involves the investigation of complexelectrical bursting patterns that are often observed inpancreatic islets and isolated beta-cells. The investigatordetermines, through mathematical modeling, whether these complexrhythms are due to oscillations in glycolysis -- that is, whetherthe coexistence of a membrane-driven bursting oscillator and anendogenous glycolytic oscillator is consistent with the publisheddata, and with data from collaborating labs. One key questionthat is addressed is whether these oscillators involvingglycolytic rhythms can be synchronized by electrical coupling.This is a necessary condition since beta-cells are electricallycoupled in islets. Finally, the effects of stochasticity throughchannel noise are investigated in both single-cell and isletmodels. Channel noise is evident in the electrical patterns ofsingle beta-cells, and suppression of this noise throughelecrical coupling may play a key role in the more regular andslower bursting patterns observed in islets. The study of pancreatic islets, composed of beta-cells, isimportant for a number of reasons. From a clinical viewpoint,they are key players in normal glucose homeostasis. Becausebeta-cells are the only cells in the body that make and secreteinsulin, their malfunction leads to type II or late-onsetdiabetes, the most prevalent form of the disease. To understandwhat makes the cells malfunction, one must first understand theirnormal functioning, which is the primary aim of this work. From abiological viewpoint, beta-cells are of great interest as thefocal point of a number of biochemical and cellular processes.They are similar in many ways to neurons, but have more complexbiochemical regulatory mechanisms. Thus, information gained fromthe study of beta-cells largely transfers over to neurons, aswell as other secretory cells. Finally, from a mathematicalviewpoint, beta-cells display rich dynamics that can only trulybe understood with the aid of mathematics. Modeling and anlysisof beta-cells has led to new mathematics, most of which can andis being applied to the study of other bursting nerve andendocrine cells. The investigator involves graduate andundergraduate students in the project, providing them withresearch opportunities at the important interface betweenbiological and mathematical sciences.