title: Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets.
abstract: Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal's ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion.
authors: Department of Mathematics, Florida State University, Tallahassee, Florida, United States of America.
authors: Joseph P
authors: JP
authors: McKenna
authors: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.
authors: Raghuram
authors: R
authors: Dhumpa
authors: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.
authors: Nikita
authors: N
authors: Mukhitov
authors: Department of Chemistry and Biochemistry and Program in Molecular Biophysics, Florida State University, Tallahassee, Florida, United States of America.
authors: Michael G
authors: MG
authors: Roper
authors: Department of Mathematics and Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, Florida, United States of America.
authors: Richard
authors: R
authors: Bertram
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D025461:Feedback, Physiological / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D008954:Models, Biological
chemical_list: D007328:Insulin; D005947:Glucose