Malaisse-Lagae F, Sener A, Malaisse W J
Biochim Biophys Acta. 1983 Feb 16;762(1):36-43. doi: 10.1016/0167-4889(83)90114-3.
Both D-glucose and its nonmetabolized analog 3-O-methyl-D-glucose are known to protect the pancreatic B-cell against the toxic action of alloxan, as if the protective action of hexoses were to involve a membrane-associated glucoreceptor site. In the present study, the protective actions of the two hexoses were found to differ from one another in several respects. Using the process of glucose-stimulated insulin release by rat pancreatic islets as an index of alloxan cytotoxicity, we observed that the protective action of D-glucose was suppressed by D-mannoheptulose and menadione, impaired by NH4Cl, and little affected by aminooxyacetate. These findings and the fact that D-glucose failed to decrease [2-14C]alloxan uptake by the islets suggest that the protective action of D-glucose depends on an increase in the generation rate of reducing equivalents (NADH and NADPH). The latter view is supported by the observation that the protective action of a noncarbohydrate nutrient, 2-ketoisocaproate, was also abolished by menadione. Incidentally, the protective action of 2-ketoisocaproate was apparently a mitochondrial phenomenon, it not being suppressed by aminooxyacetate. In contrast to that of glucose, the protective action of 3-O-methyl-D-glucose was unaffected by D-mannoheptulose, failed to be totally suppressed by menadione, and coincided with a decreased uptake of [2-14C]-alloxan by the islets. It is concluded that the protective action of D-glucose in linked to the metabolism of the sugar in islet cells, whereas that of 3-O-methyl-D-glucose results from inhibition of alloxan uptake. This conclusion reinforces our opinion that the presence in the B-cell of an alleged stereospecific membrane glucoreceptor represents a mythical concept.
已知D-葡萄糖及其非代谢类似物3-O-甲基-D-葡萄糖都能保护胰腺β细胞免受四氧嘧啶的毒性作用，就好像己糖的保护作用涉及一个与膜相关的葡萄糖受体位点。在本研究中，发现这两种己糖的保护作用在几个方面彼此不同。以大鼠胰岛葡萄糖刺激的胰岛素释放过程作为四氧嘧啶细胞毒性的指标，我们观察到D-甘露庚酮糖和甲萘醌可抑制D-葡萄糖的保护作用，NH4Cl会损害该作用，而氨氧基乙酸对其影响很小。这些发现以及D-葡萄糖未能降低胰岛对[2-14C]四氧嘧啶摄取这一事实表明，D-葡萄糖的保护作用取决于还原当量（NADH和NADPH）生成速率的增加。后一种观点得到以下观察结果的支持：非碳水化合物营养物2-酮异己酸的保护作用也被甲萘醌消除。顺便提一下，2-酮异己酸的保护作用显然是一种线粒体现象，它不受氨氧基乙酸的抑制。与葡萄糖不同，3-O-甲基-D-葡萄糖的保护作用不受D-甘露庚酮糖的影响，未被甲萘醌完全抑制，并且与胰岛对[2-¹⁴C]四氧嘧啶摄取的减少相一致。得出的结论是，D-葡萄糖的保护作用与胰岛细胞中糖的代谢有关，而3-O-甲基-D-葡萄糖的保护作用是由于抑制了四氧嘧啶的摄取。这一结论强化了我们的观点，即所谓的B细胞立体特异性膜葡萄糖受体的存在是一个虚构的概念。
