Summary
While insulin effects on the central nervous system (CNS) mediated through hypoglycaemia are well known, direct insulin effects on the CNS remain controversial. Recently, we found insulin receptors in all areas of the rat brain, with highest concentrations in the olfactory bulb, cerebral cortex and hypothalamus; all areas involved in feeding. Insulin receptors in brain were, by multiple criteria, similar to insulin receptors on classical target tissues for insulin, such as liver and fat. Insulin itself has been identified in the rat brain at concentrations on average ten times higher than in plasma. Highest concentrations were found in the olfactory bulb and hypothalamus. Brain insulin was indistinguishable from purified insulin by its behaviour in the radioimmunoassay, radioreceptor assay, bioassay and gel chromatography. In two experimental models representing extremes of plasma insulin concentrations (obese hyperinsulinaemic mice and diabetic insulinopenic rats) there were no significant changes in the concentration of insulin receptors in brain while liver receptors were modified in the expected way. This may reflect the protective influence of the blood-brain barrier or some special quality of brain insulin receptors. Insulin concentrations in brain were also unchanged in both models, which is probably indicative of the local synthesis of insulin. The role of insulin in the CNS is unknown. Besides well known metabolic actions of insulin, new roles can be postulated such as neurotransmission, neuromodulation and paracrine signalling.
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References
Williams RH, Porte D Jr (1974) The pancreas. In: Williams RH (ed), Saunders WB Textbook of endocrinology, Philadelphia, p 527
Szabo O, Szabo AJ (1972) Evidence for an insulin sensitive receptor in the central nervous system. Am J Physiol 223: 1349–1353
Woods SC, Porte D Jr (1975) Effect of intra-cisternal insulin on plasma glucose and insulin in the dog. Diabetes 24: 905–909
Storlien LH, Bellingham WP, Martin GM (1975) Localization of CNS glucoregulatory insulin receptors within the ventromedial hypothalamus. Brain Res 96: 156–160
Chowers I, Lavy S, Halpern L (1966) Effect of insulin administered intra-cisternally on the glucose level of the blood and the cerebro-spinal fluid in vagotomized dogs. Exp Neurol 14: 383–389
Margolis RU, Altszuler N (1967) Insulin in the cerebrospinal fluid. Nature 215: 1375–1376
Woods SC, Porte D Jr (1977) Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am J Physiol 233: 331–334
Oldendorf WH (1975) Permeability of the blood-brain barrier. In: Tower DB (ed) The nervous system, vol 1: The basic neurosciences. Raven Press, New Press, New York, p 279
Zimmermann EG (1979) Peptides of the brain and gut. Fed Proc 38: 2286–2353
Conlon JM, Samson WK, Dobbs RE, Orci L, Unger RH (1979) Glucagon-like polypeptides in canine brain. Diabetes 28: 700–702
Havrankova J, Roth J, Brownstein M (1978) Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272: 827–829
Van Houten M, Posner BI, Kopriwa BM, Brawer JR (1979) Insulin-binding sites in the rat brain: In vivo localization to the circumventricular organs by quantitative radio-autography. Endocrinology 105: 666–673
Kahn CR (1976) Membrane receptors for hormones and neurotransmitters. J Cell Biol 70: 261–286
Havrankova J, Roth J, Brownstein M (1979) Concentrations of insulin and of insulin receptors in the brain are independent of peripheral insulin levels: Studies of obese and streptozotocin-treated rodents. J Clin Invest 64: 636–642
Mirsky IA (1973) Insulin: isolation and purification. In: Berson SA (ed) Methods in investigative and diagnostic endocrinology, vol. 2B. Am Elsevier, New York, p 823
Havrankova J, Schmechel D, Roth J, Brownstein M (1978) Identification of insulin in rat brain. Proc Natl Acad Sci USA 75: 5737–5741
Steiner DF, Kemmler W, Clark JL, Oyer PE, Rubenstein AH (1972) The biosynthesis of insulin. In: Freinkel N, Steiner DF, (eds) Handbook of physiology, vol 1, sect 7. Williams and Wilkins, Baltimore, p 175
Dockray GJ (1977) Immunoreactive component resembling cholecystokinin octapeptide in intestine. Nature 270: 359–361
Rafaelsen OJ (1967) Insulin action on the central nervous system. Acta Med Scand [Suppl] 476: 75–84
Goodner CJ, Berne MA (1977) The failure of rat hypothalamic tissues to take up labeled insulin in vivo and to respond to insulin in vitro. Endocrinology 101: 605–612
Woods SC, Porte D Jr (1976) Insulin and set-point regulation of body weight. In: Novin D, Wyrwicka W, Bray G (eds) Hunger: Basic mechanisms and clinical implications. Raven Press, New York, p 273
Uvnäs B, Uvnäs-Wallenstein K (1978) Insulinergic nerves to the skeletal muscles of the cat? Acta Physiol Scand 103: 346–348
Pearse AGE (1977) The diffuse neuroendocrine system and the APUD concept: related “endocrine” peptides in brain, intestine, pituitary, placenta and anuran cutaneous glands. Med Biol 55: 115–125
Rosenzweig JL, Havrankova J, Lesniak MA, Brownstein MJ, Roth J (1980) Insulin is ubiquitous in extrapancreatic tissues of rats and humans. Proc Natl Acad Sci USA 77: 572–576
Karlsson FA, Grunfeld C, Kahn CR, Roth J (1979) Regulation of insulin receptors and insulin responsiveness in 3T3-L1 fatty fibroblasts. Endocrinology 104: 1383–1392
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Havrankova, J., Brownstein, M. & Roth, J. Insulin and insulin receptors in rodent brain. Diabetologia 20 (Suppl 1), 268–273 (1981). https://doi.org/10.1007/BF00254492
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DOI: https://doi.org/10.1007/BF00254492