Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice. (July 2020)

• Record Type: Journal Article
• Authors: Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Afrin, Mst Rejina; Sreedhar, Remya; Harima, Meilei; Nakamura, Masahiko; Watanabe, Kenichi; Kodama, Satoru; Fujihara, Kazuya; Sone, Hirohito
• Is Part Of: Neurochemistry international. Volume 137(2020)
• Publication Date: 2020-07
• Subjects: Brain metabolism -- GLUT 3 -- Hypoglycemia -- Insulin signaling kinases -- Ketone bodies -- Seizures; ADF Alternate day fasting -- BAD Bcl-2 associated death promoter -- BGL Blood glucose level -- CST Cell signaling technology -- EGTA Ethylene glycol tetraacetic acid -- GLUT Glucose transporter -- HCL Hydrochloride -- HMP shunt Hexose monophosphate shunt -- HRP Horseradish-peroxidase -- i.m intramuscular -- i.p intraperitoneally -- i.v intravenous -- Na2EDTA Disodium ethylenediaminetetraacetic acid -- Na3VO4 Sodium orthovanadate -- NaCl Sodium chloride -- NADPH Nicotinamide Adenine Dinucleotide Phosphate Hydrogen -- MCT Monocarboxylate transporters -- NMDA N-methyl-D-aspartate -- OGD Oxygen-glucose deprivation -- PFK 1 Phosphofructokinase 1 -- p70S6K Ribosomal protein S6 kinase -- PMSF Phenylmethylsulfonyl fluoride -- TCA cycle Tricarboxylic acid cycle -- U Unit -- USP United States Pharmacopeia; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2020.104745
• Languages: English
• ISSNs: 0197-0186

Abstract

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. Highlights: Insulin-induced moderate hypoglycemia decreases the insulin signaling kinases. Insulin-induced moderate hypoglycemia is critical to prefer ketone metabolism. Insulin-induced severe hypoglycemia may prefer glucose and ketone metabolism. 24 h Fasting may prefer ketone body metabolism. Alternate day fasting may prefer glucose and ketone body metabolism.