Glucose-stimulated Single Pancreatic Islets Sustain Increased Cytosolic ATP Levels during Initial Ca2+Influx and Subsequent Ca2+Oscillations

作者: Takashi Tanaka , Kazuaki Nagashima , Nobuya Inagaki , Hidetaka Kioka , Seiji Takashima

DOI: 10.1074/JBC.M113.499111

关键词:

摘要: In pancreatic islets, insulin secretion occurs via synchronous elevation of Ca2+ levels throughout the islets during high glucose conditions. This has two phases: a quick increase, observed after stimulus, followed by prolonged oscillations. these processes, intracellular ATP generated from is assumed to inhibit ATP-sensitive K+ channels, leading depolarization membranes, which in turn induces islets. However, little known about dynamics and their correlation with response changing levels. this study, genetically encoded fluorescent biosensor for dye were employed simultaneously monitor levels, respectively, inside single isolated We rapid increases cytosolic mitochondrial stimulation glucose, as well methyl pyruvate or leucine/glutamine. High sustained long persisted. Inhibition production suppressed initial suggesting that enhanced energy metabolism triggers phase influx. On other hand, did not fluctuate significantly level subsequent oscillation phases. Importantly, oscillations stopped immediately before decreased significantly. These results might explain how food intake evokes resulting decrease plasma leads cessation secretion.

参考文章(43)
A. Ghosh, P. Ronner, E. Cheong, P. Khalid, F.M. Matschinsky, The role of ATP and free ADP in metabolic coupling during fuel-stimulated insulin release from islet beta-cells in the isolated perfused rat pancreas. Journal of Biological Chemistry. ,vol. 266, pp. 22887- 22892 ,(1991) , 10.1016/S0021-9258(18)54437-9
Robert J. Mertz, Jennings F. Worley, Ben Spencer, John H. Johnson, Iain D. Dukes, Activation of Stimulus-Secretion Coupling in Pancreatic β-Cells by Specific Products of Glucose Metabolism Journal of Biological Chemistry. ,vol. 271, pp. 4838- 4845 ,(1996) , 10.1074/JBC.271.9.4838
P Gilon, R.M. Shepherd, J.C. Henquin, Oscillations of secretion driven by oscillations of cytoplasmic Ca2+ as evidences in single pancreatic islets. Journal of Biological Chemistry. ,vol. 268, pp. 22265- 22268 ,(1993) , 10.1016/S0021-9258(18)41522-0
Stephen J. H. Ashcroft, L. Chatra C. Weerasinghe, Philip J. Randle, Interrelationship of islet metabolism, adenosine triphosphate content and insulin release Biochemical Journal. ,vol. 132, pp. 223- 231 ,(1973) , 10.1042/BJ1320223
J. G. McCormack, A. P. Halestrap, R. M. Denton, Role of calcium ions in regulation of mammalian intramitochondrial metabolism Physiological Reviews. ,vol. 70, pp. 391- 425 ,(1990) , 10.1152/PHYSREV.1990.70.2.391
Joshua M. Baughman, Fabiana Perocchi, Hany S. Girgis, Molly Plovanich, Casey A. Belcher-Timme, Yasemin Sancak, X. Robert Bao, Laura Strittmatter, Olga Goldberger, Roman L. Bogorad, Victor Koteliansky, Vamsi K. Mootha, Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter Nature. ,vol. 476, pp. 341- 345 ,(2011) , 10.1038/NATURE10234
Isabel Goehring, Akos A. Gerencser, Sara Schmidt, Martin D. Brand, Hindrik Mulder, David G. Nicholls, Plasma Membrane Potential Oscillations in Insulin Secreting Ins-1 832/13 Cells do not Require Glycolysis and are not Initiated by Fluctuations in Mitochondrial Bioenergetics Journal of Biological Chemistry. ,vol. 287, pp. 15706- 15717 ,(2012) , 10.1074/JBC.M111.314567
Shun Terasawa, Hajime Fukuoka, Yuichi Inoue, Takashi Sagawa, Hiroto Takahashi, Akihiko Ishijima, Coordinated reversal of flagellar motors on a single Escherichia coli cell. Biophysical Journal. ,vol. 100, pp. 2193- 2200 ,(2011) , 10.1016/J.BPJ.2011.03.030
Changhong Li, Habiba Najafi, Yevgeny Daikhin, Ilana B. Nissim, Heather W. Collins, Marc Yudkoff, Franz M. Matschinsky, Charles A. Stanley, Regulation of Leucine-stimulated Insulin Secretion and Glutamine Metabolism in Isolated Rat Islets Journal of Biological Chemistry. ,vol. 278, pp. 2853- 2858 ,(2003) , 10.1074/JBC.M210577200