Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice

Research output: Contribution to journalArticle

Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Mst Rejina Afrin, Remya Sreedhar, Meilei Harima, Masahiko Nakamura, Kenichi Watanabe, Satoru Kodama, Kazuya Fujihara, Hirohito Sone

Aim and objective: Insulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. Results: Insulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. Conclusion: During hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.

Original languageEnglish (US)
Article number104745
JournalNeurochemistry International
Volume137
DOIs
StatePublished - Jul 1 2020

PMID: 32304721

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Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice. / Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Amirthalingam Thandavarayan, Rajarajan; Karuppagounder, Vengadeshprabhu; Afrin, Mst Rejina; Sreedhar, Remya; Harima, Meilei; Nakamura, Masahiko; Watanabe, Kenichi; Kodama, Satoru; Fujihara, Kazuya; Sone, Hirohito.

In: Neurochemistry International, Vol. 137, 104745, 01.07.2020.

Research output: Contribution to journalArticle

Harvard

Pitchaimani, V, Arumugam, S, Amirthalingam Thandavarayan, R, Karuppagounder, V, Afrin, MR, Sreedhar, R, Harima, M, Nakamura, M, Watanabe, K, Kodama, S, Fujihara, K & Sone, H 2020, 'Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice' Neurochemistry International, vol. 137, 104745. https://doi.org/10.1016/j.neuint.2020.104745

APA

Pitchaimani, V., Arumugam, S., Amirthalingam Thandavarayan, R., Karuppagounder, V., Afrin, M. R., Sreedhar, R., ... Sone, H. (2020). Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice. Neurochemistry International, 137, [104745]. https://doi.org/10.1016/j.neuint.2020.104745

Vancouver

Pitchaimani V, Arumugam S, Amirthalingam Thandavarayan R, Karuppagounder V, Afrin MR, Sreedhar R et al. Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice. Neurochemistry International. 2020 Jul 1;137. 104745. https://doi.org/10.1016/j.neuint.2020.104745

Author

Pitchaimani, Vigneshwaran ; Arumugam, Somasundaram ; Amirthalingam Thandavarayan, Rajarajan ; Karuppagounder, Vengadeshprabhu ; Afrin, Mst Rejina ; Sreedhar, Remya ; Harima, Meilei ; Nakamura, Masahiko ; Watanabe, Kenichi ; Kodama, Satoru ; Fujihara, Kazuya ; Sone, Hirohito. / Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice. In: Neurochemistry International. 2020 ; Vol. 137.

BibTeX

@article{2af14d1917864583877926e27046d3dc,
title = "Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice",
abstract = "Aim and objective: Insulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. Results: Insulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. Conclusion: During hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.",
keywords = "Brain metabolism, GLUT 3, Hypoglycemia, Insulin signaling kinases, Ketone bodies, Seizures",
author = "Vigneshwaran Pitchaimani and Somasundaram Arumugam and {Amirthalingam Thandavarayan}, Rajarajan and Vengadeshprabhu Karuppagounder and Afrin, {Mst Rejina} and Remya Sreedhar and Meilei Harima and Masahiko Nakamura and Kenichi Watanabe and Satoru Kodama and Kazuya Fujihara and Hirohito Sone",
year = "2020",
month = "7",
day = "1",
doi = "10.1016/j.neuint.2020.104745",
language = "English (US)",
volume = "137",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",

}

RIS

TY - JOUR

T1 - Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice

AU - Pitchaimani, Vigneshwaran

AU - Arumugam, Somasundaram

AU - Amirthalingam Thandavarayan, Rajarajan

AU - Karuppagounder, Vengadeshprabhu

AU - Afrin, Mst Rejina

AU - Sreedhar, Remya

AU - Harima, Meilei

AU - Nakamura, Masahiko

AU - Watanabe, Kenichi

AU - Kodama, Satoru

AU - Fujihara, Kazuya

AU - Sone, Hirohito

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Aim and objective: Insulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. Results: Insulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. Conclusion: During hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.

AB - Aim and objective: Insulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. Results: Insulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. Conclusion: During hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.

KW - Brain metabolism

KW - GLUT 3

KW - Hypoglycemia

KW - Insulin signaling kinases

KW - Ketone bodies

KW - Seizures

UR - http://www.scopus.com/inward/record.url?scp=85084641546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85084641546&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2020.104745

DO - 10.1016/j.neuint.2020.104745

M3 - Article

VL - 137

JO - Neurochemistry International

T2 - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

M1 - 104745

ER -

ID: 64349783