Insulin Secretion Rhythms: Calcium Regulation of Beta-Cell Metabolism and Rescue of Islet Oscillations

• Other Authors: McKenna, Joseph P. (authoraut)
• Format: Others
• Language: English; English
• Published: Florida State University
• Subjects: Applied mathematics; Biology; Endocrinology
• Online Access: http://purl.flvc.org/fsu/fd/FSU_2017SP_McKenna_fsu_0071E_13864

Pancreatic islet beta-cells play a vital role in regulating blood glucose levels by releasing insulin into the bloodstream. Insulin is released in pulses that parallel interacting beta-cell rhythms, including oscillatory glucose metabolism and periodic calcium influx. We present concurrent time series records of metabolic variables and intracellular calcium levels in glucose-stimulated beta-cells that support regulation of mitochondrial dehydrogenases is the dominant calcium feedback effect onto metabolism in the insulin secretory pathway. We include this effect into the beta-cell Dual Oscillator Model to reconcile model simulations with experimental data, then we determine the oscillation mechanism in the modified model. Islets lose the rhythms that govern insulin pulses when glucose is elevated to hyperglycemic levels. We demonstrate with modeling and experiments that oscillations lost to elevated glucose can be recovered by converting the elevated glucose stimulus to a sinusoidal wave. We predict with modeling which periodic glucose stimuli can recover islet oscillations. === A Dissertation submitted to the Department of Mathematics in partial fulfillment of the requirements for the degree of Doctor of Philosophy. === Spring Semester 2017. === April 14, 2017. === beta-cell, bifurcation, bursting, insulin, islet, oscillation === Includes bibliographical references. === Richard Bertram, Professor Directing Dissertation; Michael G. Roper, Committee Member; Ziad H. Muslimani, Committee Member; M. Nicholas J. Moore, Committee Member; Brian G. Miller, University Representative.