Feldman J M, Chapman B
Diabetologia. 1975 Dec;11(6):487-94. doi: 10.1007/BF01222097.
Using an in vitro rabbit pancreas system, we studied the effect of monoamine oxidase (MAO) inhibitors on flucose-stimulated insulin secretion. We evaluated the effect of both brief (15 min) and prolonged (60 min) exposure of pancreas segments to non-hydrazine (harmine, alpha-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 and alpha-methyltryptamine potentiated glucose-stimulated insulin secretion. Hydrazine, although not itself an MAO inhibitor, also potentiated insulin secretion. Sixty minutes of exposure to tranylcypromine or alpha-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 mumumoles/mg/min, M +/- SEM) that it has against DA (357 +/- 62.3 mumumoles/mg/min). This suggests that one reason that MAT 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.
利用体外兔胰腺系统，我们研究了单胺氧化酶（MAO）抑制剂对葡萄糖刺激的胰岛素分泌的影响。我们评估了胰腺片段短暂（15分钟）和长时间（60分钟）暴露于非肼类（哈曼、α-甲基色胺、反苯环丙胺和帕吉林）和肼类（苯乙肼、尼亚酰胺、异烟肼）MAO抑制剂的效果。所有肼类MAO抑制剂均增强了葡萄糖刺激的胰岛素分泌。在非肼类抑制剂中，只有哈曼和α-甲基色胺增强了葡萄糖刺激的胰岛素分泌。肼本身虽不是MAO抑制剂，但也增强了胰岛素分泌。暴露于反苯环丙胺或α-甲基色胺60分钟会导致胰岛素分泌减少。这些MAO抑制剂是伯胺，而伯胺可抑制胰岛素分泌。在用葡萄糖刺激前，将兔胰腺与L-3,4-二羟基苯丙氨酸（L-多巴）或5-羟色氨酸（5-HTP）孵育45分钟，可增加B细胞中的多巴胺（DA）或5-羟色胺（5-HT）含量。非肼类MAO抑制剂增加了多巴胺对胰岛素分泌的抑制作用，并且要么未改变，要么降低了5-羟色胺对胰岛素分泌的抑制作用。采用胶原酶消化技术分离兔胰岛。以5-HT和DA为底物测定胰岛匀浆的MAO活性。兔胰岛MAO对5-HT（35±8.7微摩尔/毫克/分钟，平均值±标准误）的比活性仅为对DA（357±62.3微摩尔/毫克/分钟）的十分之一。这表明MAT抑制剂不增加5-羟色胺对胰岛素分泌抑制作用的一个原因是MAO不是兔胰岛中5-HT失活的主要途径。这些研究表明，MAO抑制剂通过减少B细胞单胺降解以及不涉及MAO抑制的机制来改变胰岛素分泌。
