Insulin plays an important role in neuronal migration and neurological disorders. It signals through insulin receptors and downstream pathways like PI3K/Akt and Ras/MAPK to regulate processes like dendritic outgrowth, synaptic plasticity, and neuronal survival. Studies in C. elegans showed that insulin signaling modulates the DAF-16/FOXO transcription factor to control neuronal migration through non-autonomous effects. Chronic ethanol exposure can impair neuronal migration by inhibiting insulin signaling and reducing expression of the AAH gene involved in cell motility. While more remains unknown, insulin receptor signaling appears crucial for brain development, function and may relate to disorders like schizophrenia.

1. Insulin in
Neurogenesis
Presented by
AROGUNDADE, Tolulope
Timothy
(08/46KA015)
LECTURER: Dr. O.B.Akinola
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2. Outline
Introduction
Insulin and Properties
Insulin Receptor and Pathways
Insulin in Neuronal Migration
Insulin in Neurodegenerative Disorders
Conclusions
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3. Introduction
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4. Insulin and
Properties
Insulin is a hormone that helps to regulate the
storage of glycogen in the liver and accelerates
oxidation of sugar in cells.
Insulin is essential to maintaining brain function.
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(Ghasemi et al., 2013)

5. Where it is
Produced
The hormone
insulin is secreted by
the β cells of the
Islets of Langerhans
in the pancreas.
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6. Insulin
Receptor
The insulin receptor is a receptor tyrosine kinase well
studied with regard to its function in the regulation of
peripheral glucose metabolism.
Recent studies in neuronal cell culture suggest that
insulin receptor signaling regulates several neuronal
functions, including spine density and neurite growth.
(Choi et al., 2005)
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7. Structure of the Insulin
receptor
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(De Meyts et al., 2002)

8. Accessory
Molecules
Insulin receptor require accessory molecules known
as insulin receptor substrates (IRSs) - for example
IRS1-4- to engage multiple downstream
signaling (Withers, 2001).
Two major cellular signaling pathways,
phosphoinositide-3 kinase (PI3K)/Akt and the
Ras/mitogen-activated protein kinase (MAPK).
(Schulingkamp et al., 2000)
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9. 9
(De Meyts et al., 2002)

10. Insulin Receptor Signaling
Functions
Brain insulin receptor signaling reportedly plays
diverse roles in the CNS;
-including regulation of synaptic plasticity.
(Huang et al., 2003)
-dendritic outgrowth.
(Chen et al., 2003)
-and involvement in neuronal survival, life span ,
learning and memory, and neurological disorders.
(Steen et al., 2005)
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11. Insulin in Neuronal
Migration
Nonautonomous Regulation of Neuronal Migration
by Insulin Signaling, DAF-16/FOXO, and PAK-1.
Objective
-To demonstrate that insulin/IGF-1-PI3K signaling
pathway modulates the activity of the DAF-16/FOXO
transcription factor to regulate the anterior
migrations of the hermaphrodite-specific neurons
(HSNs) during embryogenesis of C. elegans.
(Lisa et al., 2013)
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12. Results
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(Lisa et al., 2013)

13. Summary
DAF-16 activity is required in the hypodermal
tissue of C. elegans to nonautonomously promote
the HSN migrations and that this activity relies on
the release of insulin/IGF-1-mediated inhibition of
DAF-16.
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(Lisa et al., 2013)

14. 14
Another Case
Study
Ethanol, Insulin/IGF Signaling and Neuronal Migration
-To establish that chronic gestational exposure to
ethanol impairs neuronal migration in the developing
brain, and that this effect of ethanol is associated
with reduced expression and function of a critical
target gene, aspartyl- aparaginyl beta-hydroxylase
(AAH), which has a demonstrated role in cell motility.
Objective
(De La Monte et al., 2013/2014)

15. Result
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 Ethanol exposure causes insulin and insulin-like
growth factor (IGF) resistance, inhibiting downstream
signaling through PI3K-Akt, Erk MAPK, and Cdk-5
pathways that regulate AAH mRNA.
(De La Monte et al., 2013/2014)

16. Insulin and Neurological
Diseases
Although the role that
the insulin receptor may
play in these disorders is
still a puzzle, enhanced
brain insulin receptor
signaling has been used to
treat schizophrenia patients
early in the mid-20th
century (Doroshow, 2007) .
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17. Conclusion
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 Insulin could be said to function as a motogen
and stop signal cue in neuronal migration.
Insulin signaling is required for viability,
metabolism, and synapse formation in the CNS.

18. References
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Chiu SL, Chen CM, Cline HT: Insulin receptor signaling regulates synapse number,
dendritic plasticity, and circuit function in vivo. Neuron 2008, 58:708-719.
Choi J, Ko J, Racz B, Burette A, Lee JR, Kim S, Na M, Lee HW, Kim K, Weinberg RJ,
Kim E:Regulation of dendritic spine morphogenesis by insulin receptor substrate
53, a downstream effector of Rac1 and Cdc42 small GTPases. J
Neurosci 2005, 25:869-879.
De Meyts P, Whittaker J: Structural biology of insulin and IGF1 receptors:
implications for drug design. Nat Rev Drug Discov 2002, 1:769-783.
Kanezaki Y, Obata T, Matsushima R, Minami A, Yuasa T, Kishi K, Bando Y, Uehara H,
Izumi K, Mitani T, Matsumoto M, Takeshita Y, Nakaya Y, Matsumoto T, Ebina
Y: K(ATP) channel knockout mice crossbred with transgenic mice expressing a
dominant-negative form of human insulin receptor have glucose intolerance but
not diabetes. Endocr J 2004, 51:133-144. PubMed Abstract | Publisher Full Text
White MF: Insulin signaling in health and disease. Science 2003, 302:1710-
1711. PubMed Abstract | Publisher Full Text
Withers DJ: Insulin receptor substrate proteins and neuroendocrine function.
Biochem Soc Trans 2001, 29:525-529.

19. Thank You For Listening
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