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, 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.