Metabolic and electrical oscillations: partners in controlling pulsatile insulin secretion

• Published in: American journal of physiology: endocrinology and metabolism Vol. 293; no. 4; pp. E890 - E900
• Main Authors: Bertram, Richard, Sherman, Arthur, Satin, Leslie S
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.10.2007
• Subjects: Animals; Biological Clocks - physiology; Calcium Signaling - physiology; Cells; Diabetes; Glucose - metabolism; Humans; Insulin; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - physiology; Islets of Langerhans - metabolism; Islets of Langerhans - physiology; Mathematical models; Membrane Potentials - physiology; Metabolism; Models, Biological; Pulsatile Flow - physiology; Time Factors
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00359.2007

1 Department of Mathematics and Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, Florida; 2 Laboratory of Biological Modeling, National Institutes of Health, Bethesda, Maryland; and 3 Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia Submitted 11 June 2007 ; accepted in final form 29 July 2007 Impairment of insulin secretion from the -cells of the pancreatic islets of Langerhans is central to the development of type 2 diabetes mellitus and has therefore been the subject of much investigation. Great advances have been made in this area, but the mechanisms underlying the pulsatility of insulin secretion remain controversial. The period of these pulses is 4–6 min and reflects oscillations in islet membrane potential and intracellular free Ca 2+ . Pulsatile blood insulin levels appear to play an important physiological role in insulin action and are lost in patients with type 2 diabetes and their near relatives. We present evidence for a recently developed -cell model, the "dual oscillator model," in which oscillations in activity are due to both electrical and metabolic mechanisms. This model is capable of explaining much of the available data on islet activity and offers possible resolutions of a number of longstanding issues. The model, however, still lacks direct confirmation and raises new issues. In this article, we highlight both the successes of the model and the challenges that it poses for the field. pancreatic -cells; mathematical model; diabetes Address for reprint requests and other correspondence: L. S. Satin, Dept. of Pharmacology and Toxicology, Virginia Commonwealth University, P. O. Box 980524, Richmond, VA 23298 (e-mail: lsatin{at}vcu.edu )