Adamo M, Raizada M K, LeRoith D
Section of Molecular and Cellular Physiology, NIDDK, Bethesda, MD 20892.
Mol Neurobiol. 1989 Spring-Summer;3(1-2):71-100. doi: 10.1007/BF02935589.
Insulin and the insulin-like growth factors (I and II) are homologous peptides essential to normal metabolism as well as growth. These peptide hormones are present in the brain, and, based on biosynthetic labeling studies as well as evidence for local gene expression, they are synthesized by nervous tissue as well as being taken up by the brain from the peripheral circulation. Furthermore, the presence of insulin and IGF receptors in the brain, on both neuronal and glial cells, also suggests a role for these peptides in the nervous system. Thus, these ligands affect brain electrical activity, either as neurotransmitters or as neuromodulators, altering the release and re-uptake of other neurotransmitters. The insulin and IGF-I and -II receptors found in the brain exhibit a lower molecular weight than corresponding receptors on peripheral tissues, primarily caused by alterations in glycosylation. Despite these alterations, both brain insulin and IGF-I receptors exhibit tyrosine kinase activity in cell-free systems, as do their peripheral counterparts. Brain insulin and IGF-I receptors are developmentally regulated, with the highest levels appearing in fetal or perinatal life. However, the altered glycosylation of brain receptors does not appear until late in fetal development. The receptors are widely distributed in the brain, but especially enriched in the circumventricular organs, choroid plexus, hypothalamus, cerebellum, and olfactory bulb. These studies on the insulin and IGF receptor in brain, add strong support to the suggestion that insulin and IGFs are important neuroactive substances, regulating growth, development, and metabolism in the brain.
胰岛素及胰岛素样生长因子（I和II）是对正常代谢及生长至关重要的同源肽。这些肽类激素存在于大脑中，基于生物合成标记研究以及局部基因表达的证据，它们由神经组织合成，并从外周循环进入大脑。此外，大脑中神经元和神经胶质细胞上存在胰岛素和IGF受体，这也表明这些肽在神经系统中发挥作用。因此，这些配体作为神经递质或神经调质影响大脑电活动，改变其他神经递质的释放和再摄取。大脑中发现的胰岛素、IGF-I和IGF-II受体的分子量低于外周组织中的相应受体，这主要是由糖基化改变所致。尽管有这些改变，但大脑胰岛素和IGF-I受体在无细胞系统中均表现出酪氨酸激酶活性，其外周对应物也是如此。大脑胰岛素和IGF-I受体受发育调控，在胎儿期或围生期水平最高。然而，大脑受体糖基化的改变直到胎儿发育后期才出现。这些受体在大脑中广泛分布，但在室周器官、脉络丛、下丘脑、小脑和嗅球中尤其丰富。这些关于大脑中胰岛素和IGF受体的研究，有力支持了胰岛素和IGF是重要神经活性物质、调节大脑生长、发育和代谢这一观点。
