Malaisse W J, Hutton J C, Kawazu S, Sener A
Eur J Biochem. 1978 Jun 1;87(1):121-30. doi: 10.1111/j.1432-1033.1978.tb12357.x.
Pancreatic islets contain an enzyme system which catalyzes the donation of hydrogen from NAD(P)H to menadione (2-methyl-1,4-naphthoquinone). In high concentrations (20 to 50 micrometer), menadione, in addition to lowering the concentration of reduced pyridine nucleotides in the islets, also impairs glycolysis and glucose oxidation, decreases ATP concentration, and inhibits proinsulin biosynthesis. However, at a 10 micrometer concentration, menadione fails to affect the concentration of adenine nucleotides, the utilization of glucose, the production of lactate and pyruvate, the oxidation of [6-14C]glucose and the synthesis of proinsulin; whereas the metabolism of glucose through the pentose shunt is markedly increased. The sole inhibitory effect of menadione 10 micrometer upon metabolic parameters is to reduce the concentration of both NADH and NADPH, such an effect being noticed in islets exposed to glucose 11.1 mM but not in those incubated at a higher glucose level (27.8 mM). Since, in the presence of glucose 11.1 mM, menadione 10 micrometer also severely decreases glucose-stimulated45 calcium net uptake and subsequent insulin release, it is concluded that the availability of reduced pyridine nucleotides may play an essential role in the secretory sequence by coupling metabolic to cationic events. Thus, when insulinotropic nutrients are oxidized in the B-cell, the increased availability of reduced pyridine nucleotides could modify the affinity for cations of native ionophoretic systems, eventually leading to the accumulation of calcium up to a level sufficient to trigger insulin release.
胰岛含有一种酶系统，该系统催化从NAD(P)H向甲萘醌（2-甲基-1,4-萘醌）提供氢。在高浓度（20至50微摩尔）时，甲萘醌除了降低胰岛中还原型吡啶核苷酸的浓度外，还会损害糖酵解和葡萄糖氧化，降低ATP浓度，并抑制胰岛素原的生物合成。然而，在10微摩尔的浓度下，甲萘醌不会影响腺嘌呤核苷酸的浓度、葡萄糖的利用、乳酸和丙酮酸的产生、[6-14C]葡萄糖的氧化以及胰岛素原的合成；而通过戊糖磷酸途径的葡萄糖代谢则显著增加。10微摩尔甲萘醌对代谢参数的唯一抑制作用是降低NADH和NADPH的浓度，这种作用在暴露于11.1 mM葡萄糖的胰岛中可以观察到，但在更高葡萄糖水平（27.8 mM）下孵育的胰岛中则未观察到。由于在11.1 mM葡萄糖存在的情况下，10微摩尔甲萘醌也会严重降低葡萄糖刺激的45钙净摄取和随后的胰岛素释放，因此可以得出结论，还原型吡啶核苷酸的可用性可能通过将代谢与阳离子事件耦合在分泌序列中起重要作用。因此，当促胰岛素营养物质在B细胞中被氧化时，还原型吡啶核苷酸可用性的增加可能会改变天然离子载体系统对阳离子的亲和力，最终导致钙积累到足以触发胰岛素释放的水平。
