Ca2+ oscillations in pancreatic beta-cells exposed to leucine and arginine.

Dual-wavelength microfluorometry with the fura-2 indicator was employed for continuous recordings of cytoplasmic Ca2+ (Ca2+i) in individual pancreatic beta-cells isolated from ob/ob-mice. When added to a medium containing 3 mmol l-1 glucose, both 10 mmol l-1 leucine and 20 mmol l-1 arginine induced rises in Ca2+i with periodic fluctuations. In the case of leucine, this increase was preceded by initial lowering followed by high-amplitude oscillations with a periodicity of 2-6 min. In a glucose-free medium arginine had no effect, and leucine was unable to induce more than a single peak of Ca2+i increase. When present at a concentration of 1 mmol l-1, leucine sometimes induced a couple of high-amplitude oscillations at 3 mmol l-1 glucose but lowered Ca2+i permanently in a glucose-free medium. It is likely that the high-amplitude oscillations of Ca2+i are related to the electrical activity of the beta-cells. Provided that some glucose was present, leucine initiated a similar type of Ca2+i response as obtained during glucose-induced insulin release. The observed leucine effect is therefore compatible with a role of glycolysis in generating high-amplitude Ca2+ oscillations and pulsatile insulin release.