159
Views
1
CrossRef citations to date
0
Altmetric
Review

Insulin signaling in the central nervous system, a possible pathophysiological mechanism of anesthesia-induced delayed neurocognitive recovery/postoperative neurocognitive disorder: a narrative review

, &
Pages 839-847 | Received 07 Jun 2022, Accepted 02 Nov 2022, Published online: 15 Nov 2022

References

  • Evered L, Silbert B, Knopman DS, et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth. 2018;121(5):1005–1012.
  • Needham MJ, Webb CE, Bryden DC. Postoperative cognitive dysfunction and dementia: what we need to know and do. Br J Anaesth. 2017;119(suppl_1):i115–i125.
  • Eckenhoff RG, Maze M, Xie Z, et al. Perioperative neurocognitive disorder: state of the preclinical science. Anesthesiology. 2020;132(1):55–68.
  • Evered LA, Silbert BS. Postoperative cognitive dysfunction and noncardiac surgery. Anesth Analg. 2018;127(2):496–505.
  • Evered L, Silbert B, Scott DA, et al., Recommendations for a new perioperative cognitive impairment nomenclature. Alzheimers Dement. 2019. 15(8): 1115–1116.
  • Borozdina A, Qeva E, Cinicola M, et al. Perioperative cognitive evaluation. Curr Opin Anaesthesiol. 2018;31(6):756–761.
  • Bilotta F, Qeva E, Matot I. Anesthesia and cognitive disorders: a systematic review of the clinical evidence. Expert Rev Neurother. 2016;16(11):1311–1320.
  • Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimers Dis. 2010;22(suppl_3):67–79.
  • Margolis RU, Altszuler N. Insulin in the cerebrospinal fluid. Nature. 1967;215(5108):1375–1376.
  • Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res. 2012;2012:384017.
  • Bilotta F, Lauretta MP, Tewari A, et al., Insulin and the brain: a sweet relationship with intensive care. J Intensive Care Med. 2017;32(1):48–58.
  • Unger JW, Livingston JN, Moss AM. Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog Neurobiol. 1991;36(5):343–362.
  • Stoeckel LE, Arvanitakis Z, Gandy S, et al. Complex mechanisms linking neurocognitive dysfunction to insulin resistance and other metabolic dysfunction. F1000Res. 2016;5:353.
  • Blázquez E, Velázquez E, Hurtado-Carneiro V, et al. Insulin in the brain: its pathophysiological implications for states related with central insulin resistance, type 2 diabetes and Alzheimer’s disease. Front Endocrinol (Lausanne). 2014;5:161.
  • Badenes R, Qeva E, Giordano G, et al. Intranasal insulin administration to prevent delayed neurocognitive recovery and postoperative neurocognitive disorder: a narrative review. Int J Environ Res Public Health. 2021;18(5):2681.
  • Banting FG, Best CH, Collip JB, et al. Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J. 1922;12(3):141–146.
  • Fink M, Shaw R, Gross GE, et al. Comparative study of chlorpromazine and insulin coma in therapy of psychosis. J Am Med Assoc. 1958;166(15):1846–1850.
  • Sakel M. The origin and nature of the hypoglycemic therapy of the psychoses. Bull N Y Acad Med. 1937;13(3):97–109.
  • Mack CW, Burch BO. Insulin shock therapy in dementia praecox: a report of a series of cases. Cal West Med. 1939;50(5):339–344.
  • Sonksen P, Sonksen J. Insulin: understanding its action in health and disease. Br J Anaesth. 2000;85(1):69–79.
  • Rorsman P, Braun M. Regulation of insulin secretion in human pancreatic islets. Annu Rev Physiol. 2013;75(1):155–179.
  • Watanabe M, Hayasaki H, Tamayama T, et al. Histologic distribution of insulin and glucagon receptors. Braz J Med Biol Res. 1998;31(2):243–256.
  • White MF. Insulin signaling in health and disease. Science. 2003;302(5651):1710–1711.
  • Thorens B, Mueckler M. Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab. 2010;298(2):E141–E145.
  • Schulingkamp RJ, Pagano TC, Hung D, et al., Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev. 2000. 24(8): 855–872.
  • Banks WA, Owen JB, Erickson MA. Insulin in the brain: there and back again. Pharmacol Ther. 2012;136(1):82–93.
  • Begg DP. Insulin transport into the brain and cerebrospinal fluid. Vitam Horm. 2015;98:229–248.
  • Baura GD, Foster DM, D P Jr, et al. Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. A mechanism for regulated insulin delivery to the brain. J Clin Invest. 1993;92(4):1824–1830.
  • Dorn A, Bernstein HG, Rinne A, et al. Insulin-and glucagonlike peptides in the brain. Anat Rec. 1983;207(1):69–77.
  • Wozniak M, Rydzewski B, Baker SP, et al. The cellular and physiological actions of insulin in the central nervous system. Neurochem Int. 1993;22(1):1–10.
  • Lee CC, Huang CC, Wu MY, et al. Insulin stimulates postsynaptic density-95 protein translation via the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway. J Biol Chem. 2005;280(18):18543–18550.
  • Duarte AI, Santos MS, Seic¸a R, et al. Insulin affects synaptosomal GABA and glutamate transport under oxidative stress conditions. Brain Res. 2003;977(1):23–30.
  • FT B Jr, Clarke DW, Raizada MK. Insulin inhibits specific norepinephrine uptake in neuronal cultures from rat brain. Brain Res. 1986;398(1):1–5.
  • Skeberdis VA, Lan J, Zheng X, et al. Insulin promotes rapid delivery of N-methyl-D- aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci U S A. 2001;98(6):3561–3566.
  • Lyra E, Silva NM, Lam MP, et al. Insulin resistance as a shared pathogenic mechanism between depression and type 2 diabetes. Front Psychiatry. 2019;10:57.
  • Kleinridders A, Cai W, Cappellucci L, et al. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci U S A. 2015;112(11):3463–3468.
  • Freude S, Plum L, Schnitker J, et al. Peripheral hyperinsulinemia promotes tau phosphorylation in vivo. Diabetes. 2005;54(12):3343–3348.
  • Erol A. An integrated and unifying hypothesis for the metabolic basis of sporadic Alzheimer’s disease. J Alzheimers Dis. 2008;13(3):241–253.
  • De la Monte SM, Wands JR. Alzheimer’s disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol. 2008;2(6):1101–1113.
  • Dineley KT, Jahrling JB, Denner L. Insulin resistance in Alzheimer’s disease. Neurobiol Dis. 2014;72:92–103.
  • Abbatecola AM, Paolisso G, Lamponi M, et al. Insulin resistance and executive dysfunction in older persons. J Am Geriatr Soc. 2004;52(10):1713–1718.
  • Akama KT, Van Eldik LJ. Beta-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1beta- and tumor necrosis factor-alpha (TNFalpha)-dependent, and involves a TNFalpha receptor-associated factor- and NFkappaB-inducing kinase-dependent signaling mechanism. J Biol Chem. 2000;275(11):7918–7924.
  • Carrero I, Gonzalo MR, Martin B, et al. Oligomers of β-amyloid protein (Aβ1-42) induce the activation of cyclooxygenase-2 in astrocytes via an interaction with interleukin-1β, tumour necrosis factor-α, and a nuclear factor κ-B mechanism in the rat brain. Exp Neurol. 2012;236(2):215–227.
  • Kern W, Born J, Fehm HL. Role of insulin in Alzheimer’s disease: approaches emerging from basic animal research and neurocognitive studies in humans. Drug Dev Res. 2002;56(3):511–525.
  • Feinkohl I, Winterer G, Pischon T. Diabetes is associated with risk of postoperative cognitive dysfunction: a meta-analysis. Diabetes Metab Res Rev. 2017;33(5):.
  • Kadoi Y, Saito S, Fujita N, et al. Risk factors for cognitive dysfunction after coronary artery bypass graft surgery in patients with type 2 diabetes. J Thorac Cardiovasc Surg. 2005;129(3):576–583.
  • Van Harten AE, Scheeren TWL, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012;67(3):280–293.
  • Tang N, Jiang R, Wang X, et al. Insulin resistance plays a potential role in postoperative cognitive dysfunction in patients following cardiac valve surgery. Brain Res. 2017;1657:377–382.
  • Hudetz JA, Patterson KM, Amole O, et al. Postoperative cognitive dysfunction after noncardiac surgery: effects of metabolic syndrome. J Anesth. 2011;25(3):337–344.
  • He X, Long G, Quan C, et al. Insulin resistance predicts postoperative cognitive dysfunction in elderly gastrointestinal patients. Front Aging Neurosci. 2019;11:197.
  • Hermanides J, Qeva E, Preckel B, et al. Perioperative hyperglycemia and neurocognitive outcome after surgery: a systematic review. Minerva Anestesiol. 2018;84(10):1178–1188.
  • Yang X, Zheng YT, Rong W. Sevoflurane induces apoptosis and inhibits the growth and motility of colon cancer in vitro and in vivo via inactivating Ras/Raf/MEK/ERK signaling. Life Sci. 2019;239:116916.
  • Fang X, Xia T, Xu F, et al. Isoflurane aggravates peripheral and central insulin resistance in high-fat diet/streptozocin-induced type 2 diabetic mice. Brain Res. 2020;1727:146511.
  • Chen Z, Zhang L, Liu C, et al. Effect of propofol on the skeletal muscle insulin receptor in rats with hepatic ischemia-reperfusion injury. J Int Med Res. 2020;48(4):300060519894450.
  • Restitutti F, Raekallio M, Vainionpää M, et al. Plasma glucose, insulin, free fatty acids, lactate and cortisol concentrations in dexmedetomidine-sedated dogs with or without MK-467: a peripheral α-2 adrenoceptor antagonist. Vet J. 2012;193(2):481–485.
  • Oda Y. Local anesthetic systemic toxicity: proposed mechanisms for lipid resuscitation and methods of prevention. J Anesth. 2019;33(5):569–571.
  • Maurice JM, Gan Y, Ma FX, et al. Bupivacaine causes cytotoxicity in mouse C2C12 myoblast cells: involvement of ERK and Akt signaling pathways. Acta Pharmacol Sin. 2010;31(4):493–500.
  • Beigh MA, Showkat M, Bashir B, et al. Growth inhibition by bupivacaine is associated with inactivation of ribosomal protein S6 kinase 1. Biomed Res Int. 2014;2014:831845.
  • Piegeler T, Votta-Velis EG, Bakhshi FR, et al. Endothelial barrier protection by local anesthetics: ropivacaine and lidocaine block tumor necrosis factor-α-induced endothelial cell Src activation. Anesthesiology. 2014;120(6):1414–1428.
  • Sinner B, Becke K, Engelhard K. General anaesthetics and the developing brain: an overview. Anaesthesia. 2014;69(9):1009–1022.
  • Tao G, Xue Q, Luo Y, et al. Isoflurane is more deleterious to developing brain than desflurane: the role of the Akt/GSK3β signaling pathway. Biomed Res Int. 2016;2016:7919640.
  • Liu XS, Xue QS, Zeng QW, et al. Sevoflurane impairs memory consolidation in rats, possibly through inhibiting phosphorylation of glycogen synthase kinase-3β in the hippocampus. Neurobiol Learn Mem. 2010;94(4):461–467.
  • Bi C, Cai Q, Shan Y, et al. Sevoflurane induces neurotoxicity in the developing rat hippocampus by upregulating connexin 43 via the JNK/c-Jun/AP-1 pathway. Biomed Pharmacother. 2018;108:1469–1476.
  • Brambrink AM, Evers AS, Avidan MS, et al. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology. 2010;112(4):834–841.
  • Xiao Y, Zhou L, Tu Y, et al. Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway. Neuropsychiatr Dis Treat. 2018;14:2191–2206.
  • Li GF, Li ZB, Zhuang SJ, et al. Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway. Neurosci Lett. 2018;675:152–159.
  • Bao F, Kang X, Xie Q, et al. HIF-α/PKM2 and PI3K-AKT pathways involved in the protection by dexmedetomidine against isoflurane or bupivacaine-induced apoptosis in hippocampal neuronal HT22 cells. Exp Ther Med. 2019;17(1):63–70.
  • Wang K, Zhu Y. Dexmedetomidine protects against oxygen-glucose deprivation/reoxygenation injury-induced apoptosis via the p38 MAPK/ERK signaling pathway. J Int Med Res. 2018;46(2):675–686.
  • Holscher C, van Aalten L, Sutherland C. Anaesthesia generates neuronal insulin resistance by inducing hypothermia. BMC Neurosci. 2008;9():100.
  • Werdehausen R, Fazeli S, Braun S, et al. Apoptosis induction by different local anaesthetics in a neuroblastoma cell line. Br J Anaesth. 2009;103(5):711–718.
  • Mather LE. Disposition of mepivacaine and bupivacaine enantiomers in sheep. Br J Anaesth. 1991;67(3):239–246.
  • Lirk P, Haller I, Colvin HP, et al. In vitro, inhibition of mitogen-activated protein kinase pathways protects against bupivacaine- and ropivacaine-induced neurotoxicity. Anesth Analg. 2008;106(5):1456–1464.
  • Verlinde M, Hollmann MW, Stevens MF, et al. Local anesthetic-induced neurotoxicity. Int J Mol Sci. 2016;17(3):339.
  • Mathew JP, Mackensen GB, Phillips-Bute B, et al. Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery. Stroke. 2009;40(3):880–887.
  • Voll CL, Whishaw IQ, Auer RN. Postischemic insulin reduces spatial learning deficit following transient forebrain ischemia in rats. Stroke. 1989;20(5):646–651.
  • Van der Heide LP, Ramakers GMJ, Smidt MP. Insulin signaling in the central nervous system: learning to survive. Prog Neurobiol. 2006;79(4):205–221.
  • Strong AJ, Miller SA, West IC. Protection of respiration of a crude mitochondrial preparation in cerebral ischaemia by control of blood glucose. J Neurol Neurosurg Psychiatry. 1985;48(5):450–454.
  • Robertson CS, Grossman RG. Protection against spinal cord ischemia with insulin-induced hypoglycemia. J Neurosurg. 1987;67(5):739–744.
  • LeMay DR, Gehua L, Zelenock GB, et al. Insulin administration protects neurologic function in cerebral ischemia in rats. Stroke. 1988;19(11):1411–1419.
  • Voll CL, Auer RN. Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. J Cereb Blood Flow Metab. 1991;11(6):1006–1014.
  • Tanaka M, Sawada M, Yoshida S, et al. Insulin prevents apoptosis of external granular layer neurons in rat cerebellar slice cultures. Neurosci Lett. 1995;199(1):37–40.
  • Duarte AI, Santos MS, Oliveira CR, et al. Insulin neuroprotection against oxidative stress in cortical neurons–involvement of uric acid and glutathione antioxidant defenses. Free Radic Biol Med. 2005;39(7):876–889.
  • Rensink AAM, Otte-Höller I, de Boer R, et al. Insulin inhibits amyloid beta-induced cell death in cultured human brain pericytes. Neurobiol Aging. 2004;25(1):93–103.
  • Chen Y, Run X, Liang Z, et al. Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice. Front Aging Neurosci. 2014;6:100.
  • Zhang Y, Dai CL, Chen Y, et al. Intranasal insulin prevents anesthesia-induced spatial learning and memory deficit in mice. Sci Rep. 2016;6():21186.
  • Li X, Run X, Wei Z, et al. Intranasal insulin prevents anesthesia-induced cognitive impairments in aged mice. Curr Alzheimer Res. 2019;16(1):8–18.
  • Li H, Dai CL, Gu JH, et al. Intranasal administration of insulin reduces chronic behavioral abnormality and neuronal apoptosis induced by general anesthesia in neonatal mice. Front Neurosci. 2019;13:706.
  • Yu Q, Dai CL, Zhang Y, et al. Intranasal insulin increases synaptic protein expression and prevents anesthesia-induced cognitive deficits through mTOR-eEF2 pathway. J Alzheimers Dis. 2019;70(3):925–936.
  • Lioutas VA, Alfaro-Martinez F, Bedoya F, et al. Intranasal insulin and insulin-like growth factor 1 as neuroprotectants in acute ischemic stroke. Transl Stroke Res. 2015;6(4):264–275.
  • Lioutas VA, Novak V. Intranasal insulin neuroprotection in ischemic stroke. Neural Regen Res. 2016;11(3):400–401.
  • Reger MA, Watson GS, Frey 2nd WH. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging. 2006;27(3):451–458. 2nd.
  • Avgerinos KI, Kalaitzidis G, Malli A, et al. Intranasal insulin in Alzheimer’s dementia or mild cognitive impairment: systematic review. J Neurol. 2018;265(7):1497–1510.
  • Benedict C, Frey 2nd WH, and Schiöth HB 2nd , et al. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments. Exp Gerontol. 2011;46(2–3):112–115.
  • Chapman CD, Schiöth HB, Grillo CA, et al. Intranasal insulin in Alzheimer’s disease: food for thought. Neuropharmacology. 2018;136(Pt B):196–201.
  • Claxton A, Baker LD, Hanson A, et al. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer’s disease dementia. J Alzheimers Dis. 2015;45(4):1269–1270.
  • Novak P, Pimentel Maldonado DA, Novak V. Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson's disease and multiple system atrophy: a double-blinded placebo-controlled pilot study. PLoS One. 2019;14(4):e0214364.
  • Huang Q, Li Q, Qin F, et al. Repeated preoperative intranasal administration of insulin decreases the incidence of postoperative delirium in elderly patients undergoing laparoscopic radical gastrointestinal surgery: a randomized, placebo-controlled, double-blinded clinical study. Am J Geriatr Psychiatry. 2021. 29(12): 1202–1211.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.