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 - Thandavarayan, Rajarajan Amirthalingam
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
N1 - Funding Information:
The present study was supported by Ministry of Education, Culture, Sports, Sciences and Technology, Japan and by a grant from the promotion and mutual aid corporation for private schools, Japan ( 23602012 and 26460239 ) respectively.
Publisher Copyright:
© 2020 The Authors
PY - 2020/7
Y1 - 2020/7
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
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U2 - 10.1016/j.neuint.2020.104745
DO - 10.1016/j.neuint.2020.104745
M3 - Article
C2 - 32304721
AN - SCOPUS:85084641546
SN - 0197-0186
VL - 137
SP - 104745
JO - Neurochemistry International
JF - Neurochemistry International
M1 - 104745
ER -