Abstract
Isolated canine islets of Langerhans differ from isolated islets of other species (including rodents and man) in that elevated glucose concentrations are unable to stimulate insulin secretion. Here we demonstrate that addition to the perifusate of isobutylmethylxanthine (IBMX), forskolin or 8-CPT-cAMP, all of which enhance cytosolic cAMP, permits insulin secretion in response to glucose, leucine or tolbutamide. These cAMP enhancers increase secretogogue-induced electrical activity in β-cells and restore depolarization-induced, Ca2+-dependent granule exocytosis measured as stepwise increases in membrane capacitance. We propose that the primary permissive action of cAMP is to tightly link Ca2+ entry to insulin granule release, while a secondary action is to tighten the link between glucose metabolism and cell depolarization.
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We dedicate this paper, in loving memory, to Rose Misler.
01k Carol Swanson, Amanda Raynor and Barbara Olack of the Islet Transplantation Laboratory for expert assistance in preparing canine islets; Ulises Alvarez for maintaining the islets in culture; the Radioimmunoassay Core Facility of the Diabetes Research and Training Center at Washington University (R. Gingerich, Director) for insulin determinations; Kevin D. Gillis for advice and discussions; and Debbie Windle for preparing the typescript. This work was supported by National Institutes of Health grants (DK37380) (to S.M.) and DK20579 (to D.W.S.) S.M. is an Established Investigator of the American Heart Association.
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Barnett, D.W., Pressel, D.M., Chern, H.T. et al. cAMP-enhancing agents “permit” stimulus-secretion coupling in canine pancreatic islet β-cells. J. Membarin Biol. 138, 113–120 (1994). https://doi.org/10.1007/BF00232639
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DOI: https://doi.org/10.1007/BF00232639