REGULATION OF INSULIN SECRETION STUDIED WITH PIECES OF RABBIT PANCREAS INCUBATED IN VITRO
REGULATION OF INSULIN SECRETION STUDIED WITH PIECES OF RABBIT PANCREAS INCUBATED IN VITRO
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DOI：
10.1042/bj0930066
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发表时间：
1964-01-01
影响因子：
4.1
通讯作者：
RANDLE, PJ
中科院分区：
文献类型：
--
作者：
COORE, HG;RANDLE, PJ
本文研究了各种因素对离体培养的兔胰腺片释放胰岛素速率的影响，用胰岛素抗体沉淀免疫测定法测定培养后培养基中的胰岛素浓度，并确定了引起一致反应所需的条件。浓度高于0.35-0.7 mg/ml的D-葡萄糖和D-甘露糖（3或6 mg/ml）加速胰岛素释放，但D-半乳糖、3-O-甲基-D-葡萄糖、D-果糖、D-核糖或D-葡萄糖酸钠（3 mg/ml）、D-2-脱氧葡萄糖（3或6 mg/ml）、N-乙酰基-D-葡糖胺（15 mg/ml）或D-甘露庚酮糖（3 mg/ml）不加速胰岛素释放。葡萄糖（3 mg/ml）对胰岛素释放的刺激作用可被甘露庚酮糖所消除，但不被2-脱氧葡萄糖、3-O-甲基葡萄糖、核糖和N-乙酰氨基葡萄糖所消除。在低葡萄糖浓度（0.6毫克/毫升）的胰岛素释放加速甲苯磺丁脲（200 [mu]g/ml），但不缺氧，2，4-二硝基苯酚，水杨酸，对苯二胺或吩嗪硫酸甲酯。缺氧、2，4-二硝基苯酚（250 [mu]M）、水杨酸盐（5 mM）、对苯二胺（1 mM）和吩嗪硫酸甲酯（100 [mu]M）可显著降低高葡萄糖浓度（3 mg/ml）下的胰岛素释放速率，但丙二酸盐（10 mM）不会降低胰岛素释放速率。甲苯磺丁脲的刺激作用（与葡萄糖不同）不受甘露庚酮糖的影响。葡萄糖（3 mg/ml）对胰岛素释放的刺激作用因培养基中存在谷氨酸盐、富马酸盐和丙酮酸盐而增强。在低葡萄糖浓度（0.6 mg/ml）下，这些酸和辛酸盐、乙酰乙酸盐或β-羟基丁酸盐均不影响胰岛素释放速率。葡萄糖（3 mg/ml）对胰岛素释放的刺激作用被肾上腺素（200 [mu]mg/ ml）消除，去甲肾上腺素的作用被酒石酸麦角胺（2.8 [mu]g/ml）抑制。实验结果表明，兔胰腺在体外释放胰岛素，为研究β细胞在体内的行为和研究各种因素对胰岛素分泌的影响提供了一个合适的模型。葡萄糖磷酸化和葡萄糖6-磷酸代谢途径在β-细胞中的葡萄糖诱导的胰岛素释放刺激的可能作用进行了讨论。
The effect of various factors on the rate of release of insulin from pieces of rabbit pancreas incubated in vitro has been studied by estimating the insulin concentration in the medium after incubation by immunological assay with insulin-antibody precipitate, and the conditions necessary for eliciting consistent responses have been defined. Insulin release was accelerated by D-glucose at concentrations above 0.35-0.7 mg/ml and by D-mannose (3 or 6 mg/ml), but not by D-galac-tose, 3-O-methyo-D-glucose, D-fructose, D-ribose or sodium D-gluconate (3 mg/ml), D-2-deoxyglucose (3 or 6 mg/ml), N-acetyl-D-glucosamine (15 mg/ml) or D-mannoheptulose (3 mg/ml). The stimulating effect of glucose (3 mg/ml) on insulin release was abolished by mannoheptulose but not by 2-deoxyglucose, 3-O-methylglucose, ribose or N-acetylglucosamine. Insulin release at a low glucose concentration (0.6 mg/ml) was accelerated by tolbutamide (200 [mu]g/ml) but not by anoxia, 2,4-dinitrophenol, salicylate, p-phenylenediamine or phenazine methosulphate. The rate of insulin release at a high glucose concentration (3 mg/ml) was markedly diminished by anoxia, 2,4-dinitrophenol (250 [mu]M), salicylate (5 mM), p-phenylenediamine (1 mM) and phenazine methosulphate (100 [mu]M), but not by malonate (10 mM). The stimulating effect of tolbutamide (unlike that of glucose) was not influenced by mannoheptulose. The stimulating effect of glucose (3 mg/ml) on insulin release was augmented by the presence in the medium of glutamate, fumarate and pyruvate. At a low glucose concentration (0.6 mg/ml) neither these acids nor octanoate, acetoacetate or [beta] -hydroxybutyrate influenced the rate of insulin release. The stimulating effect of glucose (3 mg/ml) on insulin release was abolished by epinephrine (200 [mu]mg/ ml), and the effect of norepinephrine was suppressed by ergotamine tartrate (2.8 [mu]g/ml). Evidence is presented that the release of insulin by rabbit pancreas in vitro provides a suitable model for the behavior of [beta] -cells in vivo and for studying the influence of various factors on insulin secretion. The possible roles of glucose phosphorylation and of pathways of metabolism of glucose 6-phosphate in [beta] -cells in the stimulation of insulin release induced by glucose are discussed.