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Adrenaline-, not somatostatin-induced hyperpolarization is accompanied by a sustained inhibition of insulin secretion in INS-1 cells. Activation of sulphonylurea K +ATP channels is not involved

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  • Transport processes, metabolism and endocrinology; kidney, gastrointestinal tract, and exocrine glands
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Abstract

Adrenaline and somatostatin inhibit insulin secretion via pertussis toxin (PTX)-sensitive mechanisms. Since glucose-stimulated release involves inhibition of ATP-sensitive K+ (K +atp ) channels and activation of Ca2+ influx, we took advantage of the glucose-sensitive, insulin-secreting cell line INS-1 to investigate whether inhibitors of insulin release modulate membrane voltage and K +atp channel activity in cellattached patch-clamp experiments. We found that adrenaline, through β2-adrenoceptors, and somatostatin counteracted glucose-induced depolarization and action potentials. As expected, these effects were mediated via PTX-sensitive G proteins since PTX pretreatment of the cells eliminated the effects of adrenaline and somatostatin on membrane voltage. When INS-1 cells were activated by adding both the K +atp channel inhibitor tolbutamide and the adenylyl cyclase activator forskolin, adrenaline and somatostatin still repolarized the plasma membrane. Single-channel measurements in the cell-attached mode revealed that tolbutamide closed a 40 to 70 pS K+ channel which was neither reopened by adrenaline nor by somatostatin. In parallel cell preparations, insulin secretion was measured by radioimmunoassay. Insulin release induced by glucose, forskolin and tolbutamide was abolished by adrenaline. In contrast, somatostatin attenuated insulin secretion by only 30%. After comparing the potency of adrenaline and somatostatin on membrane voltage and on insulin secretion, it is concluded that the repolarizing effect of adrenaline on membrane voltage is not sufficient to explain its potent inhibitory effect on insulin secretion.

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Authors and Affiliations

  1. Physiologisches Institut der Albert-Ludwigs-Universität, Hermann-Herder-Strasse 7, D-79104, Freiburg, Germany

    Kirsten-Berit Abel, Sabine Lehr & Susanne Ullrich

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  1. Kirsten-Berit Abel
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  2. Sabine Lehr
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  3. Susanne Ullrich
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Abel, KB., Lehr, S. & Ullrich, S. Adrenaline-, not somatostatin-induced hyperpolarization is accompanied by a sustained inhibition of insulin secretion in INS-1 cells. Activation of sulphonylurea K +ATP channels is not involved. Pflügers Arch — Eur J Physiol 432, 89–96 (1996). https://doi.org/10.1007/s004240050109

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  • DOI: https://doi.org/10.1007/s004240050109

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