Normal insulin secretion is oscillatory in vivo and in vitro, with a period of ∼5–10 min. The mechanism of generating these oscillations is not yet established, but a metabolic basis seems most likely for glucose-stimulated secretion. The rationale is that 1) spontaneous oscillatory operation of glycolysis is a well-established phenomenon; 2) oscillatory behavior of glycolysis involves oscillations in the ATP/ADP ratio, which can cause alternating opening and closing of ATP-sensitive K+ channels, leading to the observed oscillations in membrane potential and Ca2+ influx in pancreatic β-cells, and may also have downstream effects on exocy-tosis; 3) spontaneous Ca2+ oscillations are an unlikely basis in this case, since intracellular stores are not of primary importance in the stimulus-secretion coupling, and furthermore, insulin oscillations occur under conditions when intracellular Ca2+ levels are not changing; 4) a neural basis cannot account for insulin oscillations from perifused islets and clonai β-cells or from transplanted islets or pancreas in vivo; 5) observed oscillations in metabolite levels and fluxes further support a metabolic basis, as does the presence in β-cells of the oscillatory isoform of phosphofructokinase (PFK-M). The fact that normal oscillatory secretion is impaired in patients with NIDDM and in their near relatives suggests that such derangement may be involved in the development of the disease; furthermore, this probably reflects an early defect in the regulation and operation of the fuel metabolizing/sensing pathways of the pancreatic β-cell.
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Perspectives in Diabetes| September 01 1997
Are Metabolic Oscillations Responsible for Normal Oscillatory Insulin Secretion?
Address correspondence and reprint requests to Dr. Keith Tornheim, Boston University School of Medicine, 80 E. Concord Street, E-211, Boston, MA 02118.
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Keith Tornheim; Are Metabolic Oscillations Responsible for Normal Oscillatory Insulin Secretion?. Diabetes 1 September 1997; 46 (9): 1375–1380. https://doi.org/10.2337/diab.46.9.1375
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