Glucose induces synchronous mitochondrial calcium oscillations in intact pancreatic islets (original) (raw)

Mitochondria shape Ca 2+ signaling and exocytosis by taking up calcium during cell activation. In addition, mitochondrial Ca 2+ ([Ca 2+ ] M ) stimulates respiration and ATP synthesis. Insulin secretion by pancreatic ␤-cells is coded mainly by oscillations of cytosolic Ca 2+ ([Ca 2+ ] C ), but mitochondria are also important in excitation-secretion coupling. Here, we have monitored [Ca 2+ ] M in single ␤-cells within intact mouse islets by imaging bioluminescence of targeted aequorins. We find an increase of [Ca 2+ ] M in islet-cells in response to stimuli that induce either Ca 2+ entry, such as extracellular glucose, tolbutamide or high K + , or Ca 2+ mobilization from the intracellular stores, such as ATP or carbamylcholine. Many cells responded to glucose with synchronous [Ca 2+ ] M oscillations, indicating that mitochondrial function is coordinated at the whole islet level. Mitochondrial Ca 2+ uptake in permeabilized ␤-cells increased exponentially with increasing [Ca 2+ ], and, particularly, it became much faster at [Ca 2+ ] C > 2 M. Since the bulk [Ca 2+ ] C signals during stimulation with glucose are smaller than 2 M, mitochondrial Ca 2+ uptake could be not uniform, but to take place preferentially from high [Ca 2+ ] C microdomains formed near the mouth of the plasma membrane Ca 2+ channels. Measurements of mitochondrial NAD(P)H fluorescence in stimulated islets indicated that the [Ca 2+ ] M changes evidenced here activated mitochondrial dehydrogenases and therefore they may modulate the function of ␤-cell mitochondria. Diazoxide, an activator of K ATP , did not modify mitochondrial Ca 2+ uptake. (J. García-Sancho).