Affiliation:
1. Department of Biochemistry, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, U.K.
Abstract
Increases in mitochondrial [Ca2+] ([Ca2+]m) have recently been reported to cause long-term alterations in cellular ATP production [Jouaville, Bastianutto, Rutter and Rizzuto (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 13807Ő13812]. We have determined the importance of this phenomenon for nutrient sensing in pancreatic islets and β-cells by imaging adenovirally expressed Ca2+ and ATP sensors (aequorin and firefly luciferase). [Ca2+]m increases provoked by KCl or tolbutamide evoked an immediate increase in cytosolic and mitochondrial free ATP concentration ([ATP]c and [ATP]m respectively) at 3mM glucose. Subsequent increases in [glucose] (to 16 or 30mM) then caused a substantially larger increase in [ATP]c and [ATP]m than in naïve cells, and pre-stimulation with tolbutamide led to a larger secretory response in response to glucose. Whereas pre-challenge of islets with KCl altered the response to high [glucose] of [Ca2+]m from periodic oscillations to a sustained elevation, oscillations in [ATP]c were observed neither in naïve nor in stimulated islets. Hence, long-term potentiation of mitochondrial ATP synthesis is a central element in nutrient recognition by pancreatic islets.
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
52 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献