Recio-Pinto E, Ishii D N
Department of Anesthesiology, Medical College, Cornell University, New York, New York.
J Neurosci Res. 1988 Mar;19(3):312-20. doi: 10.1002/jnr.490190306.
The functional role of brain insulin and insulinlike growth factor (IGF) receptors is being sought. Recently it has been found that these ligands are members of a newly identified family of neuritogenic polypeptides. We studied the relationship between 125I-insulin and 125I-IGF binding and their capacity to enhance neurite formation in cultured human neuroblastoma SH-SY5Y cells. The binding of 125I-insulin was temperature-dependent and heterogeneous. The Scatchard plot and dissociation rate were both consistent with the presence of two types of sites. There appeared to be about 900 high affinity sites per cell with a Kd of about 3 nM. This compared favorably with the half-maximal concentration of 4 nM for enhancement of neurite formation. The type I IGF sites were also present. Physiologic concentrations of insulin clearly enhanced neurite formation through the insulin sites, whereas physiologic concentrations of IGF-I and IGF-II enhanced through the IGF sites. Cross-occupancy of sites was observed at supraphysiologic concentrations, providing a reasonable explanation for the broad dose-response curves for these ligands. These results support the suggestion that one function of insulin and IGF receptors in neural tissues may be to modulate neurite formation.
人们正在探寻大脑胰岛素及胰岛素样生长因子（IGF）受体的功能作用。最近发现，这些配体是新鉴定出的神经突生成多肽家族的成员。我们研究了125I-胰岛素与125I-IGF结合之间的关系，以及它们在培养的人神经母细胞瘤SH-SY5Y细胞中增强神经突形成的能力。125I-胰岛素的结合具有温度依赖性且不均一。Scatchard图和解离速率均与两种类型位点的存在一致。每个细胞似乎有大约900个高亲和力位点，解离常数（Kd）约为3 nM。这与神经突形成增强的半数最大浓度4 nM相比很有利。I型IGF位点也存在。生理浓度的胰岛素通过胰岛素位点明显增强神经突形成，而生理浓度的IGF-I和IGF-II则通过IGF位点增强。在超生理浓度下观察到位点的交叉占据，这为这些配体的宽剂量反应曲线提供了合理的解释。这些结果支持了胰岛素和IGF受体在神经组织中的一个功能可能是调节神经突形成这一观点。
