Summary
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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Lebovitz, H.E., Feldman, J.M.: Pancreatic biogenic amines and insulin secretion in health and disease. Fed. Proc.32, 1797–1802 (1973)
Cegrell, L.: The occurrence of biogenic monoamines in the mammalian endocrine pancreas. Acta physiol. scand. (suppl.)314, 1–26 (1968)
Feldman, J.M., Chapman, V.: Mechanisms of catecholamine inactivation by the endocrine pancreas. Diabetes23, 754–762 (1974)
Feldman, J.M., Chapman, B.: Characterization of pancreatic islet monoamine oxidase. Metabolism24, 581–588 (1975)
Bressler, R., Vargas-Cordon, M., Lebovitz, H.E.: Tranylcypromine: a potent insulin secretagogue and hypoglycemic agent. Diabetes17, 617–624 (1968)
Gagliardino, J.J., Hernandez, R.E., Rodriguez, R.R., Lauri, H.C.: Stimulatory effect of nialamide on serum levels of insulin. Amer. J. Physiol.219, 314–317 (1970)
Frohman, L.A.: Stimulation of insulin secretion in rats by pargyline and mebanazine. Diabetes20, 266–270 (1971)
Potter, W.Z., Zaharko, D.S., Beck, L.V.: Possible role of hydrazine group in hypoglycemia associated with the use of certain monoamine-oxidase inhibitors (MAOI's). Diabetes18, 537–541 (1969)
Lundquist, I., Ekholm, R., Ericson, I.E.: Monoamines in the pancreatic islets of the mouse, 5-hydroxytryptamine as an intracellular modifier of insulin secretion and the hypoglycemic action of the monoamine oxidase inhibitors. Diabetologia7, 414–422 (1971)
Alleyassine, H., Lee, S.H.: Inhibition by hydrazine, phenelzine and pargyline of insulin release from rat pancreas. Endocrinology89, 125–129 (1971)
Alleyassine, H., Lee, S.H.: Inhibition of insulin release by substrates and inhibitors of monoamine oxidase. Amer. J. Physiol.222, 565–569 (1972)
Feldman, J.M., Quickel, K.E., Lebovitz, H.E.: Potentiation of insulin secretion in vitro by serotonin antagonists. Diabetes21, 779–788 (1972)
Feldman, J.M., Quickel, K.E.: Effects of amino acids, epinephrine and heparin upon the radioimmunoassay of insulin in plasma. Diabetes22, 9–15 (1972)
Lacy, P.E., Kostianovsky, M.: Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes16, 35–39 (1967)
Hanks, J.H., Wallace, R.E.: Relation of oxygen and temperature in preservation of tissues by refrigeration. Proc. Soc. exp. Biol. (N. Y.)71, 196–200 (1949)
Lowry, O.H., Rosenbrough, N.J., Farr, A.L., Randall, R.J.: Protein measurement with the Folin Phenol reagent. J. biol. Chem.193, 265–275 (1951)
McCaman, R.E., McCaman, M.W., Hunt, J.M., Smith, M.S.: Micro determination of monoamine oxidase and 5-hydroxytryptophan decarboxylase activities in nervous tissues. J. Neurochem.12, 15–23 (1965)
Zar, J.H.: Biostatistical Analysis. N. J.: Prentice-Hall Englewood Cliffs 1974
Zirkle, C.L., Kaiser, C.: Monoamine oxidase inhibitors (non-hydrazines) In: Psychopharmicological Agents, vol. I. (ed. M. Gordon) pp. 445–554. New York: Academic Press 1964
Gylfe, E., Hellman, B., Sehlin, J., Taljedal, I.B.: Amino acid conversion into 5-hydroxytryptamine in pancreatic B-cells. Endocrinology93, 932 (1973)
Hagen, P.: Observations on the substrate specificity of dopa decarboxylase from adrenal medulla, human pheochromocytoma and human argentaffinoma. Brit. J. Pharmacol.18, 175–182 (1962)
Cegrell, L., Falck, B., Hellman, B.: Monoaminergic mechanisms in the endocrine pancreas. In: The structure and metabolism of pancreatic islets (eds. S.E. Brolin, B. Hellman, H. Knutson) pp. 429–435. Oxford: Pergamon Press 1964
Cegrell, L.: Monoaminergic mechanisms in the pancreaticα-cells. In: The structure and metabolism of the pancreatic islets (eds. S. Falkner, B. Hellman, I.B. Taljedal) pp. 131–140. Oxford: Pergamon Press 1970
Hellman, B., Lernmark, A., Sehlin, J., Taljedal, I.B.: Transport and storage of 5-hydroxytryptamine in pancreatic B-cells. Biochem. Pharmacol.21, 695–706 (1972)
Feldman, J.M., Lebovitz, H.E.: A serotoninergic mechanism for the control of insulin secretion. Trans. Ass. Amer. Physcns.85, 279–294 (1972)
Quickel, K.E., Feldman, J.M., Lebovitz, H.E.: Inhibition of insulin secretion by serotonin and dopamine: species variation. Endocrinology89, 1295–1302 (1971)
Udenfriend, S., Witkop, B., Redfield, B.G., Weissbach, H.: Studies with reversible inhibitors of monoamine oxidase: harmaline and related compounds. Biochem. Pharmacol.1, 160–165 (1958)
Greig, M.E., Walk, R.A., Gibbons, A.J.: The effect of three tryptamine derivatives on serotonin metabolism in vitro and in vivo. J. Pharmacol. exp. Ther.127, 110–115 (1959)
Maxwell, D.R., Gray, W.R., Taylor, E.M.: Relative activity of some inhibitors of monoamine oxidase in potentiating the action of tryptaminein vitro andin vivo. Brit. J. Pharmacol.17, 310–320 (1961)
Hendley, E., Snyder, S.S.: Relationship between the action of monoamine oxidase inhibitors on the noradrenaline uptake system and their antidepressant efficacy. Nature220, 1330–1331 (1968)
Gomes, B., Igaue, I., Kloepfer, H.G., Yasunobu, K.T.: Amine oxidase XIV. Isolation and characterization of the multiple beef liver amine oxidase components. Arch. Biochem.132, 16–27 (1969)
Feldman, J.M., Lebovitz, H.E.: Structural determinants of catecholamine action onin vitro insulin release. J. Pharmacol, exp. Ther.176, 611–621 (1971)
Feldman, J.M., Lebovitz, H.E.: Structural determinants of indole amine action on in vitro insulin release. Endocrinology91, 809–816 (1972)
Blaschko, H.: Amine oxidase and amine metabolism. Pharmacol. Rev.4, 415–458 (1952)
Gatgounis, J.: Structural activity relationships of a series of amines injected before and after monoamine oxidase inhibitor. Arch. int. Pharmacodyn.154, 412–420 (1965)
McIsaac, W.M., Page, I.H.: The metabolism of serotonin (5-hydroxytryptamine). J. Biol. Chem.234, 858–864 (1959)
Kakimoto, Y., Armstrong, M.D.: On the identification of octopamine in mammals. J. Biol. Chem.237, 422–427 (1962)
Author information
Authors and Affiliations
Additional information
Supported by the Veterans Administration (2650-1).
Rights and permissions
About this article
Cite this article
Feldman, J.M., Chapman, B. Monoamine oxidase inhibitors: Nature of their interaction with rabbit pancreatic islets to alter insulin secretion. Diabetologia 11, 487–494 (1975). https://doi.org/10.1007/BF01222097
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01222097