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Rhythm of the beta-cell oscillator is not governed by a single regulator: multiple systems contribute to oscillatory behavior

By Emma Heart and Peter J.S. Smith


Pulsatile insulin output, paralleled by oscillations in intracellular Ca(2+), reflect oscillating metabolism within beta-cells in response to secretory fuels. Here we question whether oscillatory periodicity is conserved or varied from stimulation to stimulation, whether glycolysis is essential for the manifestation of an oscillatory response, and if an environment of nutrient oversupply affects oscillatory regularity. We have determined that a beta-cell oscillatory Ca(2+) pattern is independent of the type of applied secretory fuel (glucose, methyl-pyruvate, or alpha-ketoisocaproate). In addition, single cells respond with the same pattern when repeatedly stimulated, regardless of the type of stimulatory fuel. Presence of substimulatory glucose is not necessary to obtain an oscillatory responses to methyl-pyruvate or alpha-ketoisocaproate. Glucose-6-phosphate, as a measure of glycolytic flux, is not detectable under these conditions. These data suggest that multiple systems, rather than a single enzyme component, can contribute to the beta-cell oscillatory behavior. Prolonged exposure to high levels of palmitate impaired oscillatory regularity in the individual beta-cells. This supports the hypothesis that a high-fat environment might contribute to loss of regular oscillatory pattern in diabetic subjects, acting, at least in part, at the level of the single beta-cel

Topics: QH301
Year: 2007
OAI identifier:
Provided by: e-Prints Soton

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  1. (1972). A collection of metabolite assays. In: A Flexible System of Enzymatic Analysis. doi
  2. (2005). Adenine nucleotide regulation in pancreatic beta-cells: modeling of ATP/ADP-Ca2 interactions. doi
  3. (1990). Allosteric regulation, cooperativity, and biochemical oscillations. doi
  4. (1997). Are metabolic oscillations responsible for normal oscillatory insulin secretion? doi
  5. (2004). Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 53: S119–S124, doi
  6. (1998). Biothermokinetics in the post genomic era. In:
  7. (2003). Citrate oscillates in liver and pancreatic beta cell mitochondria and in INS-1 insulinoma cells. doi
  8. (1996). Control of frequency and amplitude is shared by all enzymes in three models for yeast glycolytic oscillations. doi
  9. (1979). Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. doi
  10. (1999). Deficiency of phosphofructo-1-kinase/muscle subtype in humans is associated with impairment of insulin secretory oscillations. doi
  11. (2000). Differential regulation of [Ca2]i oscillations in mouse pancreatic islets by glucose, alpha-ketoisocaproic acid, glyceraldehyde and glycolytic intermediates. doi
  12. (2003). Dihydroxyacetone-induced oscillations in cytoplasmic free Ca2 and the ATP/ADP ratio in pancreatic beta-cells at substimulatory glucose. doi
  13. (1985). Do pancreatic islet contain significant amount of phosphoenolpyruvate carboxykinase or ferroactivator activity? doi
  14. (2000). External signals and internal oscillation dynamics: principal aspects and response of stimulated rhythmic processes. In: Self-Organized Biological Dynamics and Nonlinear Control, edited by Wallezcek J. Cambridge, UK: doi
  15. (1977). glucagon, and glucose exhibit synchronous sustained oscillations in fasting monkeys. doi
  16. Glucose modulates [Ca2]i oscillations in pancreatic islets via ionic and glycolytic mechanisms. doi
  17. (2006). Glucosedependent increase in mitochondrial membrane potential, but not cytoplasmic calcium, correlates with insulin secretion in single islet cells.
  18. (1997). Individual beta cells within the intact islet differentially respond to glucose. doi
  19. (1996). Insulinotropic action of methylpyruvate: secretory, cationic, and biosynthetic aspects. doi
  20. (1969). Islet-cell metabolism during insulin release.
  21. (1992). Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets. doi
  22. (1992). Long-term regulation of pancreatic B-cell responsiveness to D-glucose by food availability, feeding schedule, and diet composition. doi
  23. (2006). Low-carbohydrate and high-fat intake among adult patients with poorly controlled type 2 diabetes mellitus. doi
  24. (1980). Mechanism of glucose-induced insulin secretion. doi
  25. (2002). Metabolic oscillations in -cells. doi
  26. (1993). Metabolism of the insulin secretagogue methyl succinate by pancreatic islets. doi
  27. (2003). Modeling of Ca2 flux in pancreatic beta-cells: role of the plasma membrane and intracellular stores.
  28. (1984). Nutrient metabolism in islet cells. doi
  29. (1996). Oscillations in activities of enzymes in pancreatic islet subcellular fractions induced by physiological concentration of effectors. doi
  30. (1997). Oscillations in oxygen consumption by permeabilized clonal pancreatic beta-cells (HIT) incubated in an oscillatory glycolyzing muscle extract. doi
  31. (2006). Oscillations of cyclic AMP in hormone-stimulated insulin-secreting beta-cells. doi
  32. (2000). Pathophysiology of impaired pulsatile insulin release. doi
  33. (1965). Phase relationship of glycolytic intermediates in yeast cells with oscillatory metabolic control. doi
  34. (1995). Phosphofructokinase isoenzymes in pancreatic islets and clonal beta-cells (INS-1). doi
  35. (1991). Pulsatile insulin delivery has greater metabolic effects than continuous hormone administration in man: importance of pulse frequency. doi
  36. (1993). Pulsatile insulin has greater hypoglycemic effect than continuous delivery. doi
  37. (2006). Simultaneous optical measurements of cytosolic Ca2 and cAMP in single cells.
  38. Slave’ metabolites and enzymes. A rapid way of delineating metabolic control. doi
  39. (1995). Slow [Ca2]i oscillations induced by ketoisocaproate in single mouse pancreatic islets. doi
  40. (2006). Stimulation of insulin release by glyceraldehyde may not be similar to glucose. doi
  41. (2005). Substrate effects on oscillations in metabolism, calcium and secretion in single mouse islets of Langerhans. doi
  42. (1976). Taljedal IB. The dynamics of insulin release from mouse pancreatic islet cells in suspension. Pflu ¨gers Arch 366: 185–188, doi
  43. (2000). Triggering and amplifying pathways of regulation of insulin secretion by glucose. doi
  44. (2007). Yeast glycolytic oscillations that are not E1299 doi
  45. (2007). Yeast glycolytic oscillations that are not E1299MULTISYSTEM doi

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