A nutrient-regulated cytosolic calcium oscillator in endocrine pancreatic glucagon-secreting cells

We investigated the influence of nutrients on spontaneous cytosolic calcium oscillations in InR1-G9 glucagonoma cells, a model for pancreatic alpha-ce lls. The oscillations depended on calcium release from stores and on calciu m influx, partly through voltage-dependent calcium channels. Oscillations r equired the presence of at least 1 mM glucose, 50 mu M alanine, or 50 mu M glutamine, but were terminated by higher nutrient concentrations (40 mM glu cose, or above 2 mM alanine or glutamine). The effects depended on the meta bolism of the nutrients. Glutamine and alanine hyperpolarized the cells. Th is effect was inhibited (glutamine) or attenuated (alanine) by 1 mM ouabain . Our findings suggest that [Ca2+](i) regulation in alpha-cells is dominate d by slow oscillations induced by a lack of metabolic energy, resulting in decreased calcium export and storage, as well as increased calcium in flux, partly due to depolarization caused by reduced sodium pump activity. These processes, leading to an elevated cytosolic calcium concentration, may med iate oscillations by calcium-induced calcium release from intracellular sto res.