INSULIN IN THE CEREBROSPINAL-FLUID

The presence, distribution and specific localization of insulin and its receptors in the central nervous system (CNS) have been described in numerous reports. Insulin in the CNS appears to be similar to pancreatic insulin by biochemical and immunological criteria. While the presence of insulin in the cerebrospinal fluid (CSF)-an essential neurohumoral transport system-has been widely reported, the available information is fragmented and therefore it is difficult to determine the significance of insulin in the CSF and to establish future research directions. This paper presents an integrative view of the studies concerning insulin in the CSF of various species including the human. Evidence suggests that insulin in the CSF and brain may be the result of local synthesis in the CNS, and uptake from the peripheral blood through the blood-brain barrier and circumventricular organs. The passage of insulin from the peripheral blood through the blood-brain barrier may be mediated by a specific transport system coupled to insulin receptors in cerebral microvessels. The transfer of insulin from the peripheral blood through the circumventricular organs is not specific and may depend on simple diffusion. Slow access of insulin to brain interstitial fluid adjacent to the blood-brain barrier and circumventricular organs may be followed by selective transport to other brain sites and into the ventricular-subarachnoideal CSF. It has been hypothesized that the choroid plexuses, which constitute the blood-CSF interface, might be a nonspecific pathway for rapid insulin transport into the CSF. Insulin may also pass from the CSF into the peripheral blood via absorption into the arachnoid villi. This evidence indicates that insulin may be transported in both directions between the CSF-brain and the peripheral blood. Evidence also suggests that the presence of insulin in the CSF is of pivotal importance for its neurophysiological or neuropathophysiological significance.