title: Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.
abstract: Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.
authors.affiliation: Neuroscience Post-Graduation Program, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Krista Minéia
authors.initials: KM
authors.lastname: Wartchow
authors.affiliation: State University of Rio Grande do Sul (UERGS), Benjamin Constant, 229, Bento Gonçalves, Rio Grande do Sul, 95700-000, Brazil. ana-tramontina@uergs.edu.br.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Tramontina
authors.affiliation: Biochemistry Post-Graduation Program, UFRGS, Porto Alegre, Brazil.
authors.forename: Daniela F
authors.initials: DF
authors.lastname: de Souza
authors.affiliation: Biochemistry Post-Graduation Program, UFRGS, Porto Alegre, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: Biasibetti
authors.affiliation: Biochemistry Post-Graduation Program, UFRGS, Porto Alegre, Brazil.
authors.forename: Larissa D
authors.initials: LD
authors.lastname: Bobermin
authors.affiliation: Neuroscience Post-Graduation Program, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.|Biochemistry Post-Graduation Program, UFRGS, Porto Alegre, Brazil.
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007328:Insulin; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D005947:Glucose
keywords: Astrocyte; Glucose metabolism; Insulin; MAPK; RAGE; S100B