Cyclic AMP potentiates glucose‐induced insulin release from mouse pancreatic islets without increasing cytosolic free Ca2

RORSMAN P. & ABRAHAMSSON, H. 1985. Cyclic AMP potentiates glucose‐induced insulin release from mouse pancreatic islets without increasing cytosolic free Ca2+. Acta Physiol Scand 125, 639–647. Received 18 March 1985, accepted 28 May 1985. ISSN 0001–6772. Department of Medical Cell Biology, Biomedicum, University of Uppsala, Sweden. The effects of various stimulants of insulin release on cytosolic free Ca2+, [Ca2+]i, in dispersed and cultured pancreatic β‐cells from ob/ob‐mice were studied using the indicator quin‐2, which in itself has only slight effects on the glucose‐induced insulin release and the metabolism of the sugar. The resting [Ca2+]i was 158 ± 7 nM. After increasing glucose to 20 mM there was a lag‐period of 1–2 min before [Ca2+]i gradually rose, reaching a new plateau 60% higher after 5–6 min. Increasing intracellular cyclic AMP by adding forskolin did not further increase [Ca2+]i; on the contrary there was a slight temporary reduction despite a doubling of insulin secretion. The maintenance of the β‐cell function was evident from a marked increase of cytosolic [Ca2+]i after depolarization evoked by high extracellular K+. Also dibutyryl cyclic AMP and theophylline lacked the ability to raise [Ca2+]i beyond that obtained by glucose. The results suggest that cyclic AMP potentiates glucose‐induced insulin release by sensitizing the secretory machinery to changes of [Ca2+]i rather than by increasing the cytosolic concentration of the ion.