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Title: Glucose-stimulated single pancreatic islets sustain increased cytosolic ATP levels during initial Ca(2+) influx and subsequent Ca(2+) oscillations.
Authors: Tanaka, Takashi
Nagashima, Kazuaki  kyouindb  KAKEN_id
Inagaki, Nobuya  kyouindb  KAKEN_id
Kioka, Hidetaka
Takashima, Seiji
Fukuoka, Hajime
Noji, Hiroyuki
Kakizuka, Akira  kyouindb  KAKEN_id
Imamura, Hiromi  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 稲垣, 暢也
垣塚, 彰
今村, 博臣
Keywords: ATP
Energy Metabolism
Pancreatic Islets
Issue Date: 24-Jan-2014
Publisher: American Society for Biochemistry and Molecular Biology
Journal title: The Journal of biological chemistry
Volume: 289
Issue: 4
Start page: 2205
End page: 2216
Abstract: In pancreatic islets, insulin secretion occurs via synchronous elevation of Ca(2+) levels throughout the islets during high glucose conditions. This Ca(2+) elevation has two phases: a quick increase, observed after the glucose stimulus, followed by prolonged oscillations. In these processes, the elevation of intracellular ATP levels generated from glucose is assumed to inhibit ATP-sensitive K(+) channels, leading to the depolarization of membranes, which in turn induces Ca(2+) elevation in the islets. However, little is known about the dynamics of intracellular ATP levels and their correlation with Ca(2+) levels in the islets in response to changing glucose levels. In this study, a genetically encoded fluorescent biosensor for ATP and a fluorescent Ca(2+) dye were employed to simultaneously monitor the dynamics of intracellular ATP and Ca(2+) levels, respectively, inside single isolated islets. We observed rapid increases in cytosolic and mitochondrial ATP levels after stimulation with glucose, as well as with methyl pyruvate or leucine/glutamine. High ATP levels were sustained as long as high glucose levels persisted. Inhibition of ATP production suppressed the initial Ca(2+) increase, suggesting that enhanced energy metabolism triggers the initial phase of Ca(2+) influx. On the other hand, cytosolic ATP levels did not fluctuate significantly with the Ca(2+) level in the subsequent oscillation phases. Importantly, Ca(2+) oscillations stopped immediately before ATP levels decreased significantly. These results might explain how food or glucose intake evokes insulin secretion and how the resulting decrease in plasma glucose levels leads to cessation of secretion.
Description: インスリン分泌における重要因子が変動する様子を可視化 -蛍光タンパク質センサーを用いたライブイメージング法で-. 京都大学プレスリリース. 2014-01-30.
Rights: This research was originally published in [The Journal of Biological Chemistry, 289, 2205-2216. doi: 10.1074/jbc.M113.499111 January 24, 2014]. © the American Society for Biochemistry and Molecular Biology.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1074/jbc.M113.499111
PubMed ID: 24302735
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