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Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism

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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-3H-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.

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Acknowledgments

This study was supported by the National Council for Scientific and Technological Development (CNPq, Brazil), Ministry of Education (MEC/CAPES, Brazil), State Foundation for Scientific Research of Rio Grande do Sul (FAPERGS), and National Institute of Science and Technology for Excitotoxicity and Neuroprotection (MCT/INCTEN).

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Authors and Affiliations

  1. Neuroscience Post-Graduation Program, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil

    Krista Minéia Wartchow & Carlos-Alberto Gonçalves

  2. State University of Rio Grande do Sul (UERGS), Benjamin Constant, 229, Bento Gonçalves, Rio Grande do Sul, 95700-000, Brazil

    Ana Carolina Tramontina

  3. Biochemistry Post-Graduation Program, UFRGS, Porto Alegre, Brazil

    Daniela F. de Souza, Regina Biasibetti, Larissa D. Bobermin & Carlos-Alberto Gonçalves

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  1. Krista Minéia Wartchow
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  2. Ana Carolina Tramontina
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  4. Regina Biasibetti
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  5. Larissa D. Bobermin
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Correspondence to Ana Carolina Tramontina.

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Wartchow, K.M., Tramontina, A.C., de Souza, D.F. et al. Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism. Neurochem Res 41, 1420–1429 (2016). https://doi.org/10.1007/s11064-016-1851-y

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  • DOI: https://doi.org/10.1007/s11064-016-1851-y

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