Sener A, Hutton J C, Kawazu S, Boschero A C, Somers G, Devis G, Herchuelz A, Malaisse W J
J Clin Invest. 1978 Oct;62(4):868-78. doi: 10.1172/JCI109199.
NH4+ caused a dose-related, rapid, and reversible inhibition of glucose-stimulated insulin release by isolated rat islets. It also inhibited glyceraldehyde-, Ba2+-, and sulfonylurea-stimulated insulun secretion. NH4+ failed to affect glucose utilization and oxidation, glucose-stimulated proinsulin biosynthesis, the concentration of ATP, AD, and AMP, and the intracellular pH. NH4+ also failed to affect the ability of theophylline and cytochalasin B to augment glucose-induced insulin release. However, in the presence and absence of glucose, accumulation of NH4+ in islet cells was associated with a fall in the concentration of NADH and HADPH and a concomitant alteration of 86Rb+ and 45Ca2+ (or 133Ba2+) handling. These findings suggest that reduced pyridine nucleotides, generated by the metabolism of endogenous of exogenous nutrients, may modulate ionophoretic processes in the islet cells and by doing so, affect the net uptake of Ca2+ and subsequent release of insulin.
NH4+对分离的大鼠胰岛葡萄糖刺激的胰岛素释放产生剂量相关的、快速且可逆的抑制作用。它还抑制甘油醛、Ba2+和磺脲类刺激的胰岛素分泌。NH4+不影响葡萄糖利用和氧化、葡萄糖刺激的胰岛素原生物合成、ATP、AD和AMP的浓度以及细胞内pH。NH4+也不影响茶碱和细胞松弛素B增强葡萄糖诱导的胰岛素释放的能力。然而，无论有无葡萄糖存在，胰岛细胞中NH4+的积累都与NADH和HADPH浓度的下降以及86Rb+和45Ca2+（或133Ba2+）转运的相应改变有关。这些发现表明，由内源性或外源性营养物质代谢产生的还原型吡啶核苷酸可能调节胰岛细胞中的离子载体过程，进而影响Ca2+的净摄取和随后的胰岛素释放。
