EFFECT OF SUGARS ON (PRO)INSULIN BIOSYNTHESIS
EFFECT OF SUGARS ON (PRO)INSULIN BIOSYNTHESIS
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DOI：
10.1042/bj1740517
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发表时间：
1978-01-01
影响因子：
4.1
通讯作者：
HEDESKOV, CJ
中科院分区：
文献类型：
--
作者：
ASHCROFT, SJH;BUNCE, J;HEDESKOV, CJ
测定了[4，5 - 3 H]亮氨酸掺入胰岛素加胰岛素原（称为胰岛素原）和大鼠胰岛总蛋白的速率。葡萄糖刺激总蛋白和（原）胰岛素生物合成的速率，但（原）胰岛素生物合成的刺激优先。甘露糖和N-乙酰葡糖胺也刺激（原）胰岛素和总蛋白的生物合成;肌苷和二羟丙酮刺激（原）胰岛素的生物合成特异性。果糖不刺激（原）胰岛素的生物合成时，单独测试，但这样做的存在下，低浓度的葡萄糖，甘露糖或N-乙酰葡糖胺。许多葡萄糖类似物不刺激（原）胰岛素生物合成。甘露庚酮糖抑制由葡萄糖或甘露糖刺激的（原）胰岛素和总蛋白质的合成，但不抑制由二羟丙酮、肌苷或N-乙酰葡糖胺刺激的（原）胰岛素和总蛋白质的合成;根皮素（9 μ M）优先抑制N-乙酰葡糖胺刺激的（原）胰岛素生物合成。相同的葡萄糖传感器机制可能控制胰岛素的释放和生物合成，并建议底物位点模型。刺激（原）胰岛素和总蛋白生物合成的阈值低于葡萄糖刺激胰岛素释放的阈值;此外，对葡萄糖浓度升高的生物合成反应慢于胰岛素释放。这些研究结果的生理意义进行了讨论。咖啡因和异丁基甲基黄嘌呤，在已知的浓度增加胰岛3“：5”-环AMP和增强葡萄糖诱导的胰岛素释放，对葡萄糖刺激的（原）胰岛素生物合成的速率没有影响。
Rates of incorporation of [4,5-3H]leucine into insulin plus proinsulin, designated (pro)insulin, and total protein in rat pancreatic islets were measured. Glucose stimulates rates of total protein and (pro)insulin biosynthesis, but (pro)insulin biosynthesis was stimulated preferentially. Mannose and N-acetylglucosamine also stimulated (pro)insulin and total protein biosynthesis; inosine and dihydroxyacetone stimulated (pro)insulin biosynthesis specifically. Fructose did not stimulate (pro)insulin biosynthesis when tested alone, but did so in the presence of low concentrations of glucose, mannose or N-acetylglucosamine. Many glucose analogs did not stimulate (pro)insulin biosynthesis. Mannoheptulose inhibited synthesis of (pro)insulin and total protein stimulated by glucose or mannose but not by dihydroxyacetone, inosine or N-acetylglucosamine; phloretin (9 .mu.M) inhibited N-acetylglucosamine-stimulated (pro)insulin biosynthesis preferentially. The same glucose-sensor mechanism may control both insulin release and biosynthesis, and a substrate-site model is suggested. The threshold for stimulation of biosynthesis of (pro)insulin and total protein was lower than that found for glucose-stimulated insulin release; moreover, the biosynthetic response to an elevation of glucose concentration was slower than that found for insulin release. The physiological implication of these findings is discussed. Caffeine and isobutylmethylxanthine, at concentrations known to increase islet 3'':5''-cyclic AMP and potentiated glucose-induced insulin release, were without effect on rates of glucose-stimulated (pro)insulin biosynthesis.