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Monoamine oxidase inhibitors: Nature of their interaction with rabbit pancreatic islets to alter insulin secretion

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Using an in vitro rabbit pancreas system, we studied the effect of monoamine oxidase (MAO) inhibitors on glucose-stimulated insulin secretion. We evaluated the effect of both brief (15 min) and prolonged (60 min) exposure of pancreas segments to non-hydrazine (harmine,α-methyltryptamine, tranylcypromine and pargyline) and hydrazine (phenelzine, nialamide, iproniazid) type MAO inhibitors. All of the hydrazine type MAO inhibitors potentiated glucose-stimulated insulin secretion. Of the non-hydrazine inhibitors, only harmine andα-methyltryptamine potentiated glucose-stimulated insulin secretion. Hydrazine, although not itself an MAO inhibitor, also potentiated insulin secretion. Sixty minutes of exposure to tranylcypromine orα-methyltryptamine caused a decrease in insulin secretion. These MAO inhibitors are primary amines and primary amines can inhibit insulin secretion. The dopamine (DA) or serotonin (5-HT) content of the B-cells was increased by incubating rabbit pancreas with L-3,4-dihydroxyphenylalanine (L-Dopa) or 5-hydroxytryptophan (5-HTP) for forty-five minutes prior to stimulation with glucose. Non-hydrazine MAO inhibitors increased dopamine inhibition of insulin secretion and either did not alter, or decreased serotonin inhibition of insulin secretion. Rabbit pancreatic islets were isolated using the collagenase digestion technique. The MAO activity of islet homogenates was determined using 5-HT and DA as substrates. Rabbit islet MAO has only one-tenth the specific activity against 5-HT (35±8.7 μμmoles/mg/ min, M±SEM) that it has against DA (357±62.3 μμmoles/mg/ min). This suggests that one reason that MAO inhibitors do not increase serotonin inhibition of insulin secretion is because MAO is not the major pathway for 5-HT inactivation in rabbit pancreatic islets. These studies suggest that MAO inhibitors alter insulin secretion, by both decreasing B-cell monoamine degradation and by mechanisms that do not involve MAO inhibition.

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Authors and Affiliations

  1. Durham Veterans Administration Hospital and Division of Endocrinology, Dept. of Medicine, Duke Univ. Medical Center, Durham, North Carolina, USA

    J. M. Feldman & B. Chapman

Authors
  1. J. M. Feldman
  2. B. Chapman

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Supported by the Veterans Administration (2650-1).

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