AccScience Publishing / ITPS / Volume 4 / Issue 2 / DOI: 10.36922/itps.v4i2.43
REVIEW

Role of Insulin in Brain: An Emphasis on Molecular Functions

Snehashis Kundu1 Sayeed Mohammed Firdous2
Show Less
1 National Institute of Pharmaceutical Education and Research Guwahati, Changsari, Assam, India
2 Department of Pharmacology, Calcutta Institute of Pharmaceutical Technology and AHS, Howrah, West Bengal, India
INNOSC Theranostics and Pharmacological Sciences 2021, 4(2), 17–21; https://doi.org/10.36922/itps.v4i2.43
Submitted: 8 March 2022 | Accepted: 23 May 2022 | Published: 30 June 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Insulin signaling in brain has emerged as a recent field of research since decreased brain insulin levels were linked to impaired learning, memory, and neurodegenerative diseases like Alzheimer’s disease. Brain insulin has a pivotal role in regulating glucose metabolism, memory, learning, neuron formation, and to be neuroprotective through a cascade of cellular signaling process. In addition, insulin may serve as a promising therapy against diabetes and neurodegeneration conditions. Interestingly, insulin has been also faced as the potential missing link between neurodegenerative disorders and diabetes. Therefore, this review aims to untangle the complex interactions among aging and diabetes which allow the development of more effective therapeutic strategies to conquer neurodegenerative condition as well as diabetes.

Keywords
Insulin
Memory
Learning
Neurodegenerative diseases
Aging
Diabetes
References
[1]

Satyanarayana, U.; Chakrapani, U. Biochemistry Book. 5th ed. New Delhi: Elsevier Publisher, 2017. p. 641–2.

[2]

Bliss, M. The History of Insulin. Diabetes Care, 1993, 16(3), 4–7. 

[3]

Zhao, W.; Chen, H.; Xu, H. Brain Insulin Receptors and Spatial Memory. Correlated Changes in Gene Expression, Tyrosine Phosphorylation, and Signaling Molecules in the Hippocampus of Water Maze Trained Rats. J. Biol. Chem., 1999, 274(49), 34893–902. 

[4]

Salkovic-Petrisic, M.; Hoyer, S. Central Insulin Resistance as a Trigger for Sporadic Alzeheimer-Like Pathology: An Experimental Approach. J. Neural Transm., 2007, 72, 217–33. 

[5]

Zhao, W.Q.; Chen, H.; Quon, M.J.; Alkon, D.L. Insulin and the Insulin Receptor in the Experimental Models of Learning and Memory. Eur. J. Pharmacol., 2004, 490(1-3), 71–81.

[6]

Baskin, D.G.; Sipols, A.J.; Schwartz, M.W.; White, M.F. Immunocytochemical Detection of Insulin Receptor Substrate-1 (IRS-1) in Rat Brain: Colocalization with Phosphotyrosine. Regul. Pept., 1993, 48(1-2), 257–66. 

[7]

Schwartz, M.W.; Figlewicz, D.P.; Baskin, D.G.; Woods, S.C.; Porte, D. Jr. Insulin in the Brain: A Hormonal Regulation of Energy Balance. Endocr. Rev., 1992, 13(3), 387–414. 

[8]

Marks, J.L.; King, M.G.; Baskin, D.G. Insulin and Insulin- Like Growth Factors in Molecular Biology and Physiology of Insulin and Insulin-Like Growth Factors. Adv. Exp. Med. Biol., 1991, 293, 459–70. 

[9]

Unger, J.W.; Moss, A.M.; Livingston, J.N. Immunohistochemical Localization of Insulin Receptors and Phosphotyrosine in the Brainstem of the Adult Rat. Neurosci., 1991, 42(3), 853–61. 

[10]

Marks, J.L.; Maddison, J.; Eastman, C.J. Subcellular Localization of Rat Brain Insulin Binding Sites. J. Neurochem., 1988, 50(30), 774-781.

[11]

Schulingkamp, R.J.; Pagan, T.C.; Hung, D.; Raffa, R.B. Insulin Receptors and Insulin Action in The Brain: Review and Clinical Implications. Neurosci. Biobehav. Rev., 2000, 24(8), 855–72. 

[12]

Wada, A.; Yokoo, H.; Yanagita, T.; Kobayashi, H. New Twist on Neuronal Insulin Receptor Signaling in Health, Disease, and Therapeutics. J. Pharmacol. Sci., 2005, 99(2), 128–43.

[13]

Moloney, A.M.; Griffin, R.J.; Timmons, S.; O’Connor, R.; Ravid, R.; O’Neill, C. Defects in IGF-1 Receptor, Insulin Receptor and IRS1/2 in Alzheimer’s Disease Indicate Possible Resistance to IGF-1 and Insulin Signaling. Neurobiol. Aging, 2010, 31(2), 224–43. 

[14]

Van der Heide, L.P.; Ramakers, G.M.J.; Smidt, M.P. Insulin Signaling in the Central Nervous System: Learning to Survive. Prog. Neurobiol., 2006, 79(4), 205–21.

[15]

Erol, A. An Integrated and Unifying Hypothesis for the Metabolic Basis of Sporadic Alzheimer’s Disease. J. Alzheimer’s Dis., 2008, 13(3), 241–53.

[16]

Ogata, T.; Iijima, S.; Hoshikawa, S. Opposing Extracellular Signal-Regulated Kinase and Akt Pathways Control Schwann Cell Myelination. J. Neurosci., 2004, 24(30), 6724–32. 

[17]

Johnson-Farly, N.N.; Travkina, T.; Cowen, D.S. Cumulative Activation of Akt and Consequent Inhibition of Glycogen Synthase Kinase-3 by Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor-1 in Cultured Hippocampal Neurons. J. Pharmacol. Exp. Ther., 2006, 316(3), 1062–9.

[18]

Hetman, M.; Kanning, K.; Cavanaugh, J.E.; Xia, Z. Neuroprotection by Brain- Derived Neurotrophic Factor is Mediated by Extracellular Signal-Regulated Kinase and Phosphatidyalinositol 3-Kinase. J. Biol. Chem., 1999, 274(32), 22569–80. 

[19]

Gasparini, L.; Xu, H. Potential Role of Insulin and IGF-1 in Alzheimer’s Disease. Trends Neurosci., 2003, 26(8), 404–6. 

[20]

Santos, M.S.; Pereira, E.M.; Carvaho, A.P. Stimulation of Immunoreactive Insulin Release by Glucose in the Rat Brain Synaptosomes. Neurochem. Res., 1999, 24(1), 33–6. 

[21]

Shah, B.H.; Hausman, R.E. Effect of Insulin on GABAergic Development in the Embryonic Chick Retina. Brain Res. Dev. Brain Res., 1993, 72(2), 151–8. 

[22]

Yang, J.W.; Raizada, M.K.; Fellows, R.E. Effects of Insulin on Cultured Rat Brain Cells: Stimulation of Ornithine Decarboxylase Activity. J. Neurochem., 1981, 36(3), 1050–7. 

[23]

Levin, B.E. Factors Promoting and Ameliorating the Development of Obesity. Physiol. Behav., 2005, 86(5), 633–9. 

[24]

Levin, B.E. Metabolic Sensing Neurons and Control of Energy Homeostasis. Physiol. Behav., 2006, 89(4), 486–9.

[25]

Plum, L.; Belgardt, B.F.; Bruning, J.C. Central Insulin Action in Energy and Glucose Homeostasis. J. Clin. Invest., 2006, 116(7), 1761–3. 

[26]

Bingham, E.M.; Hopkins, D.; Smith, D. The Role of Insulin in Human Brain Glucose Metabolism: An 18fluorodeoxyglucose Positron Emission Tomography Study. Diabetes, 2002, 51(12), 169–78. 

[27]

Ghosh, A.; Yuk, Y.C.; Mansfield, B.C.; Chou, J.Y. Brain Contains a Functional Glucose 6-Phosphate Complex Capable of Endogenous Glucose Production. J. Biol. Chem., 2005, 280(12): 11114–9. 

[28]

Russell, J.W.; Golovoy, D.; Vincent, A.M. High Glucose- Induced Oxidative Stress and Mitochondrial Dysfunction in Neurons. FASEB J., 2002, 16(13), 1738–48.

[29]

Kern, W.; Peters, A.; Fruehwald-Schultes, B.; Deininger, E.; Born, J.; Fehm, H.L. Improving Influence of Insulin on Cognitive Functions in Humans. Neuroendocrinol, 2001, 74(4), 270–80. 

[30]

Boyd, F.T.; Clarke, D.W.; Raizada, M.K. Insulin Inhibits Specific Norepinephrineuptake in Neuronal Cultures from Rat Brain. Brain Res., 1986, 398(10), 1–5.

[31]

Barbaccia, M.L.; Chuang, D.M.; Costa E. Is Insulin are Neuromodulator? Adv. Biochem. Psychopharmacol., 1982, 33, 511–8.

[32]

Duarte, A.I.; Santos, M.S.; Seica, R.; Oliveira, C.R. Oxidative Stress Effects Synaptosomal Γ-Amino Butyric Acid and Glutamate Transport in Diabetic Rats: The Role of Insulin. Diabetes, 2004, 53(8), 2110–6.

[33]

Duarte, A.I.; Santos, M.S.; Seica, R.; de Oliveira C.R. Insulin Affects Synaptosomal GABA and Glutamate Transport Under Oxidative Stress Condition. Brain Res., 2003, 977(1), 23–30. 

[34]

Duarte, A.I.; Santos, P.; Oliveira, C.R.; Santos, M.S.; Rego, A.C. Insulin Neuroprotection against Oxidative Stress is Mediated by Akt and GSK-3β Signaling Pathways and Changes in Protein Expression. Biochem. Biophys. Acta. 2008., 1783(6), 994–1002

[35]

Chin, P.C.; Majdzadeh, N.; D’Mello, S.R. Inhibition of GSK 3β is a Common Event in Neuroprotection by Different Survival Factors. Mol. Brain Res., 2005, 137(1-2), 193–210. 

[36]

Leinnimger, G.M.; Backus, C.; Uhler, M.D.; Lentz, S.I.; Feldman, E.L. Phosphotidylinositol 3-Kinase and Akt Effectors Mediate Insulin-Like Growth Factor-I Neuroprotection in Dorsal Root Ganglia Neurons. FASEB J., 2004, 18(13), 1544–6. 

[37]

Ryu, B.R.; Ko, H.W.; Jou, I.; Noh, J.S.; Gwag, B.J. Phosphatidylinositol3- Kinase- Mediated Regulation of Neuronal Apoptosis and Necrosis by Insulin and IGF-I. J. Neurobiol., 1999, 39(4), 536–6.

[38]

Noh, K.M.; Lee, J.C.; Ahn, Y.H.; Hong, S.H.; Koh, J.Y. Insulin- Induced Oxidative Neuronal Injury in Cortical Culture: Mediation by Induced N- Methyl-D-Aspartate Receptors. IUBMB Life, 1999, 48(3), 263–9.

Conflict of interest
No conflict of interest declared.
Share
Back to top
INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing