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Ca2+ Controls Slow NAD(P)H Oscillations in Glucose-stimulated Mouse Pancreatic Islets

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Journal J Physiol
Specialty Physiology
Date 2006 Feb 4
PMID 16455690
Citations 61
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Abstract

Exposure of pancreatic islets of Langerhans to physiological concentrations of glucose leads to secretion of insulin in an oscillatory pattern. The oscillations in insulin secretion are associated with oscillations in cytosolic Ca(2+) concentration ([Ca(2+)](c)). Evidence suggests that the oscillations in [Ca(2+)](c) and secretion are driven by oscillations in metabolism, but it is unclear whether metabolic oscillations are intrinsic to metabolism or require Ca(2+) feedback. To address this question we explored the interaction of Ca(2+) concentration and islet metabolism using simultaneous recordings of NAD(P)H autofluorescence and [Ca(2+)](c), in parallel with measurements of mitochondrial membrane potential (DeltaPsi(m)). All three parameters responded to 10 mm glucose with multiphasic dynamics culminating in slow oscillations with a period of approximately 5 min. This was observed in approximately 90% of islets examined from various mouse strains. NAD(P)H oscillations preceded those of [Ca(2+)](c), but their upstroke was often accelerated during the increase in [Ca(2+)](c), and Ca(2+) influx was a prerequisite for their generation. Prolonged elevations of [Ca(2+)](c) augmented NAD(P)H autofluorescence of islets in the presence of 3 mm glucose, but often lowered NAD(P)H autofluorescence of islets exposed to 10 mm glucose. Comparable rises in [Ca(2+)](c) depolarized DeltaPsi(m). The NAD(P)H lowering effect of an elevation of [Ca(2+)](c) was reversed during inhibition of mitochondrial electron transport. These findings reveal the existence of slow oscillations in NAD(P)H autofluorescence in intact pancreatic islets, and suggest that they are shaped by Ca(2+) concentration in a dynamic balance between activation of NADH-generating mitochondrial dehydrogenases and a Ca(2+)-induced decrease in NADH. We propose that a component of the latter reflects mitochondrial depolarization by Ca(2+), which reduces respiratory control and consequently accelerates oxidation of NADH.

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References
1.
McCormack J, Longo E, Corkey B . Glucose-induced activation of pyruvate dehydrogenase in isolated rat pancreatic islets. Biochem J. 1990; 267(2):527-30. PMC: 1131320. DOI: 10.1042/bj2670527. View

2.
McCormack J, Halestrap A, Denton R . Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev. 1990; 70(2):391-425. DOI: 10.1152/physrev.1990.70.2.391. View

3.
Ashcroft F, Rorsman P . Electrophysiology of the pancreatic beta-cell. Prog Biophys Mol Biol. 1989; 54(2):87-143. DOI: 10.1016/0079-6107(89)90013-8. View

4.
Chou H, Berman N, Ipp E . Oscillations of lactate released from islets of Langerhans: evidence for oscillatory glycolysis in beta-cells. Am J Physiol. 1992; 262(6 Pt 1):E800-5. DOI: 10.1152/ajpendo.1992.262.6.E800. View

5.
Misler S, Barnett D, Falke L . Effects of metabolic inhibition by sodium azide on stimulus-secretion coupling in B cells of human islets of Langerhans. Pflugers Arch. 1992; 421(2-3):289-91. DOI: 10.1007/BF00374842. View