Insulin regulates astrocytic glucose handling through cooperation with IGF-I

Ana M. Fernandez, Edwin Hernandez-Garzón, Paloma Perez-Domper, Alberto Perez-Alvarez, Sara Mederos, Takashi Matsui, Andrea Santi, Angel Trueba-Saiz, Lucía García-Guerra, Julia Pose-Utrilla, Jens Fielitz, Eric N. Olson, Ruben Fernandez De La Rosa, Luis Garcia Garcia, Miguel Angel Pozo, Teresa Iglesias, Alfonso Araque, Hideaki Soya, Gertrudis Perea, Eduardo D. MartinIgnacio Torres Aleman

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes.

Original languageEnglish (US)
Pages (from-to)64-74
Number of pages11
JournalDiabetes
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Fernandez, A. M., Hernandez-Garzón, E., Perez-Domper, P., Perez-Alvarez, A., Mederos, S., Matsui, T., Santi, A., Trueba-Saiz, A., García-Guerra, L., Pose-Utrilla, J., Fielitz, J., Olson, E. N., De La Rosa, R. F., Garcia, L. G., Pozo, M. A., Iglesias, T., Araque, A., Soya, H., Perea, G., ... Aleman, I. T. (2017). Insulin regulates astrocytic glucose handling through cooperation with IGF-I. Diabetes, 66(1), 64-74. https://doi.org/10.2337/db16-0861