Figlewicz D P, Bentson K, Ocrant I
Department of Psychology, University of Washington, Seattle.
Brain Res Bull. 1993;32(4):425-31. doi: 10.1016/0361-9230(93)90210-3.
We have previously reported that insulin can enhance endogenous noradrenergic activity in vitro in the rat CNS. In the present study, we examined one potential mechanism underlying this effect: the ability of insulin to inhibit norepinephrine (NE) reuptake and secondarily increase its synaptic concentration. Acute (20 min) insulin treatment (0.1-10 nM) significantly inhibited specific 3H-norepinephrine uptake by rat hypothalamic slices. To ascertain whether this is a direct effect of insulin on cells that can synthesize and release norepinephrine, we studied NE uptake by the rat pheochromocytoma PC12 cell line. In PC12 cells, insulin (0.5-10 nM) inhibited NE uptake whereas the related peptide, insulin-like growth factor 1 (IGF-1), did not. Insulin did not compete with 3H-mazindol (a ligand for the NE reuptake transporter) binding to PC12 cell membranes. Thus, this effect of insulin is not due to interaction with either IGF-1 receptors or the norepinephrine transporter, but may be due to insulin interaction with its own receptor. Chronic (96-h) insulin treatment of PC12 cells also resulted in an inhibition of 3H-norepinephrine uptake, and membranes prepared from cells chronically treated with insulin bound less 3H-desipramine than control membranes. Thus, chronic insulin treatment may result in a decrease in the numbers of membrane-associated transporters. We conclude that insulin has a direct and physiological role in the modulation of synaptic norepinephrine levels by modulating reuptake by cells that synthesize and release norepinephrine.
我们之前曾报道，胰岛素可在体外增强大鼠中枢神经系统内源性去甲肾上腺素能活性。在本研究中，我们探讨了这一效应背后的一种潜在机制：胰岛素抑制去甲肾上腺素（NE）再摄取并继而增加其突触浓度的能力。急性（20分钟）胰岛素处理（0.1 - 10 nM）显著抑制了大鼠下丘脑切片对特异性3H-去甲肾上腺素的摄取。为确定这是否是胰岛素对能够合成和释放去甲肾上腺素的细胞的直接作用，我们研究了大鼠嗜铬细胞瘤PC12细胞系对NE的摄取。在PC12细胞中，胰岛素（0.5 - 10 nM）抑制NE摄取，而相关肽胰岛素样生长因子1（IGF-1）则无此作用。胰岛素不与3H-马吲哚（一种NE再摄取转运体的配体）竞争结合PC12细胞膜。因此，胰岛素的这一作用并非由于与IGF-1受体或去甲肾上腺素转运体相互作用，而可能是由于胰岛素与其自身受体相互作用。对PC12细胞进行慢性（96小时）胰岛素处理也导致3H-去甲肾上腺素摄取受到抑制，并且由长期接受胰岛素处理的细胞制备的膜与对照膜相比，结合的3H-地昔帕明更少。因此，慢性胰岛素处理可能导致膜相关转运体数量减少。我们得出结论，胰岛素通过调节合成和释放去甲肾上腺素的细胞的再摄取，在调节突触去甲肾上腺素水平方面具有直接的生理作用。
