Mitochondrial priming modifies Ca2+ oscillations and insulin secretion in pancreatic islets

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, 13807-13812]. We have determined the importance of this phenomenon for nutrient sensing in pancreatic islets and beta -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 3 mM glucose. Subsequent increases in [glucose] (to 16 or 30 mM) then caused a substantially larger Increase In [ATP](c) and [ATP](m) than in naive cells, and prestimulation 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 naive nor in stimulated islets. Hence? longterm potentiation of mitochondrial ATP synthesis is a central element in nutrient recognition by pancreatic islets.