Phantom Bursting Models and Complex Bursting Patterns in Pancreatic Islets

Florida State University, Tallahassee FL

Investigators

Abstract

Bertram The investigator and his colleagues study the behavior of insulin-secreting pancreatic beta-cells. These cells display a wide range of complex dynamics that are best understood with the aid of mathematical modeling and analysis. The investigator has recently developed a new mathematical model for beta-cells that postulates an intracellular calcium subspace compartment located between the endoplasmic reticulum and the cell membrane. This model is based on recent data from a collaborating lab, and is being further developed as new experiments are performed. One direction of development involves the investigation of complex electrical bursting patterns that are often observed in pancreatic islets and isolated beta-cells. The investigator determines, through mathematical modeling, whether these complex rhythms are due to oscillations in glycolysis -- that is, whether the coexistence of a membrane-driven bursting oscillator and an endogenous glycolytic oscillator is consistent with the published data, and with data from collaborating labs. One key question that is addressed is whether these oscillators involving glycolytic rhythms can be synchronized by electrical coupling. This is a necessary condition since beta-cells are electrically coupled in islets. Finally, the effects of stochasticity through channel noise are investigated in both single-cell and islet models. Channel noise is evident in the electrical patterns of single beta-cells, and suppression of this noise through elecrical coupling may play a key role in the more regular and slower bursting patterns observed in islets. The study of pancreatic islets, composed of beta-cells, is important for a number of reasons. From a clinical viewpoint, they are key players in normal glucose homeostasis. Because beta-cells are the only cells in the body that make and secrete insulin, their malfunction leads to type II or late-onset diabetes, the most prevalent form of the disease. To understand what makes the cells malfunction, one must first understand their normal functioning, which is the primary aim of this work. From a biological viewpoint, beta-cells are of great interest as the focal point of a number of biochemical and cellular processes. They are similar in many ways to neurons, but have more complex biochemical regulatory mechanisms. Thus, information gained from the study of beta-cells largely transfers over to neurons, as well as other secretory cells. Finally, from a mathematical viewpoint, beta-cells display rich dynamics that can only truly be understood with the aid of mathematics. Modeling and anlysis of beta-cells has led to new mathematics, most of which can and is being applied to the study of other bursting nerve and endocrine cells. The investigator involves graduate and undergraduate students in the project, providing them with research opportunities at the important interface between biological and mathematical sciences.