Ashcroft S J, Crossley J R, Crossley P C
Biochem J. 1976 Mar 15;154(3):701-7. doi: 10.1042/bj1540701.
The effects of N-acylglucosamines on insulin release have been studied. N-Acylglucosamines stimulated insulin release from rat islets in vitro only if a sub-stimulatory concentration of glucose was also present, and this secretory response was abolished by mannoheptulose. In perifused islets the rapidity of the secreotry response to N-acetyl-D-glucosamine was similar to that observed with D-glucose. Increasing acyl-chain length from N-acetyl- to N-hexanoyl-D-glucosamine impaired the secretory response; however, N-dichloroacetyl-D-glucosamine was a more potent stimulator of release than was N-acetyl-D-glucosamine. Polymers of N-acetyl-D-glucosamine containing two to six monomers linked alpha1-4 did not stimulate insulin release; glucosamine linked to dextran via a propionyl or hexanoyl spacer group was also without insulin-releasing ability. N-Acylglucosamines were also effective in eliciting insulin release in vivo when injected into conscious rats. At the dose used (86 mumol), N-acetylgucosamine elicited a rapid rise in plasma-insulin concentration; N-butyrylglucosamine was less effective, and there was little or no response to N-hexanoylglucosamine. The response to N-dichloroacetyl-glucosamine was greater than that to N-acetylglucosamine; an increase in plasma insulin concentration could be elicited by N-dichloroacetylglucosamine at a dose (17 mumol) at which neither glucose nor N-acetylglucosamine was effective. The secretory response to acetylglucosamine is not mediated by conversion into glucose. Rates of (pro)-insulin biosynthesis by rat islets have been measured (Pro)-insulin biosynthesis was stimulated by glucose, and this response was abolished by mannoheptulose. N-Acetylglucosamine also stimulated (pro)-insulin biosynthesis; this effect of N-acetylglucosamine did not require the presence of glucose, and was not abolished by mannoheptulose. It is concluded that there are differences in signal reception and/or transduction for the processes of insulin biosynthesis and release.
已对N-酰基葡糖胺对胰岛素释放的影响进行了研究。只有在存在亚刺激浓度葡萄糖的情况下，N-酰基葡糖胺才能在体外刺激大鼠胰岛释放胰岛素，且这种分泌反应会被甘露庚酮糖消除。在灌流胰岛中，对N-乙酰-D-葡糖胺的分泌反应速度与对D-葡萄糖观察到的相似。从N-乙酰-D-葡糖胺增加酰基链长度至N-己酰-D-葡糖胺会损害分泌反应；然而，N-二氯乙酰-D-葡糖胺比N-乙酰-D-葡糖胺是更强效的释放刺激剂。含有两个至六个通过α1-4连接的单体的N-乙酰-D-葡糖胺聚合物不刺激胰岛素释放；通过丙酰基或己酰基间隔基团与葡聚糖连接的葡糖胺也没有胰岛素释放能力。当注射到清醒大鼠体内时，N-酰基葡糖胺在体内引发胰岛素释放方面也有效。在所使用的剂量（86 μmol）下，N-乙酰葡糖胺引起血浆胰岛素浓度迅速升高；N-丁酰葡糖胺效果较差，对N-己酰葡糖胺几乎没有反应。对N-二氯乙酰葡糖胺的反应大于对N-乙酰葡糖胺的反应；N-二氯乙酰葡糖胺在剂量（17 μmol）下可引起血浆胰岛素浓度升高，而在此剂量下葡萄糖和N-乙酰葡糖胺均无效。对乙酰葡糖胺的分泌反应不是由转化为葡萄糖介导的。已测量了大鼠胰岛（前）胰岛素生物合成速率。（前）胰岛素生物合成受到葡萄糖刺激，且这种反应被甘露庚酮糖消除。N-乙酰葡糖胺也刺激（前）胰岛素生物合成；N-乙酰葡糖胺的这种作用不需要葡萄糖存在，且不被甘露庚酮糖消除。得出的结论是，胰岛素生物合成和释放过程在信号接收和/或转导方面存在差异。
