Jain K, Logothetopoulos J
Biochem J. 1978 Mar 15;170(3):461-7. doi: 10.1042/bj1700461.
Inosine, guanosine and adenosine strongly stimulated proinsulin biosynthesis and insulin secretion in isolated mouse pancreatic islets. None of the purine ribonucleosides stimulated insulin secretion in rat islets, although as reported [jain & Logothetopoulos (1977) Endocrinilogy 100, 923-927] inosine and guanosine, but no adenosine, were potent stimulants of proinsulin biosynthesis in this species. The purine bases had no effect in either species. D-Ribose, which enhanced proinsulin biosynthesis at 0.3 and 0.6 mM but not at 5mM in rat pancreatic islets [jain & Logothetopoulos (1977) Endocrinology 100, 923-927], produced no secretory signals in rat islets and was without any effect on proinsulin biosynthesis and insulin secretion in mouse islets. The rates of oxidation of 14C-labelled purine ribonucleosides and D-ribose in islets of the two species correlated well with their effectiveness as inducers of insulin secretion and proinsulin biosynthesis. Specific inhibitors of purine ribonucleoside phosphorylase, adenosine deaminiase and of purine ribonucleoside transport suppressed the stimulatory effects of nucleosides in pancreatic islets without altering the effect of D-glucose. The same inhibitors also markedly diminished the oxidation rats of the labelled purine ribonucleosides. The experiments clearly indicate that porinsulin biosynthesis and insulin secretion are modulated through metabolic signals and not through interactions of intact substrate molecules with cell receptors.
肌苷、鸟苷和腺苷能强烈刺激分离的小鼠胰岛中胰岛素原的生物合成及胰岛素分泌。尽管如文献报道[贾恩和洛戈泰托普洛斯（1977年），《内分泌学》100卷，923 - 927页]，肌苷和鸟苷（而非腺苷）是大鼠胰岛中胰岛素原生物合成的有效刺激物，但这些嘌呤核糖核苷均不能刺激大鼠胰岛分泌胰岛素。嘌呤碱基对这两种动物的胰岛均无作用。D - 核糖在大鼠胰岛中，于0.3和0.6 mM时能增强胰岛素原的生物合成，但在5 mM时则无此作用[贾恩和洛戈泰托普洛斯（1977年），《内分泌学》100卷，923 - 927页]，它在大鼠胰岛中未产生分泌信号，且对小鼠胰岛的胰岛素原生物合成和胰岛素分泌没有任何影响。两种动物胰岛中14C标记的嘌呤核糖核苷和D - 核糖的氧化速率，与其作为胰岛素分泌和胰岛素原生物合成诱导剂的有效性密切相关。嘌呤核糖核苷磷酸化酶、腺苷脱氨酶及嘌呤核糖核苷转运的特异性抑制剂，可抑制核苷对胰岛的刺激作用，而不改变D - 葡萄糖的作用。同样这些抑制剂也显著降低了标记嘌呤核糖核苷在大鼠中的氧化速率。这些实验清楚地表明，胰岛素原生物合成和胰岛素分泌是通过代谢信号调节的，而非通过完整底物分子与细胞受体的相互作用来调节。
