AMINO ACID-INDUCED [CA2-MOUSE PANCREATIC-ISLETS OF LANGERHANS(](I) OSCILLATIONS IN SINGLE)

1. The effects of amino acids on cytosolic free calcium concentration ([Ca2+](i)) were measured, using fura-2 fluorescence imaging, in mouse pancreatic islets of Langerhans. 2. Slow [Ca2+](i) oscillations appea red when isolated islets were incubated with a solution containing a m ixture of amino acids and glucose at concentrations found in the plasm a of fed animals. 3. In the presence of 11 mM glucose, alanine (5 mM) and arginine (10 mM) induced a transient rise in [Ca2+](i) followed by an oscillatory pattern, while leucine (3 mM) and isoleucine (10 mM) t riggered the appearance of slow [Ca2+](i) oscillations. 4. Also in the presence of glucose (11 mM), tolbutamide (10 mu M) increased the dura tion of the glucose-induced [Ca2+](i) oscillations. While tolbutamide (10 mu M) did not modify the leucine-induced slow oscillatory pattern, addition of diazoxide (10 mu M) resulted in the gradual appearance of [Ca2+](i) oscillations which resembled the glucose-induced fast oscil lations. 5. Like stimulatory glucose concentrations (11 mM), glycerald ehyde (10 mM) induced fast oscillations of [Ca2+](i). 6. Fluoroacetate (2 mM) transformed leucine-induced slow [Ca2+](i) oscillations into f ast [Ca2+](i) oscillations. Iodoacetate (1 mM) completely inhibited an y oscillatory pattern. 7. It is suggested that mitochondrially generat ed signals, derived from amino acid oxidative metabolism, acting in co njunction with glucose-signalled messengers, are very effective at clo sing ATP-dependent K+ channels (K-ATP(+)). 8. We propose that metaboli c regulation of K-ATP(+) channels is one of the mechanisms underlying the modulation of the oscillatory [Ca2+](i) response to nutrient secre tagogues.