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Insulin regulates astrocytic glucose handling through cooperation with IGF-I

Item Type:Article
Title:Insulin regulates astrocytic glucose handling through cooperation with IGF-I
Creators Name:Fernandez, A.M. and Hernandez-Garzón, E. and Perez-Domper, P. and Perez-Alvarez, A. and Mederos, S. and Matsui, T. and Santi, A. and Trueba-Saiz, A. and Garcia-Guerra, L. and Pose-Utrilla, J. and Fielitz, J. and Olson, E.N. and Fernandez de la Rosa, R. and Garcia Garcia, L. and Pozo, M.A. and Iglesias, T. and Araque, A. and Soya, H. and Perea, G. and Martin, E.D. and Torres Aleman, I.
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.
Keywords:Astrocytes, Biological Transport, Glucose, Glucose Transporter Type 1, Glycogen, Immunoassay, Insulin, Insulin-Like Growth Factor I, Lactic Acid, Neurons, Plasmids, Polymerase Chain Reaction, Positron-Emission Tomography, Animals, Mice
Publisher:American Diabetes Association
Page Range:64-74
Date:January 2017
Official Publication:https://doi.org/10.2337/db16-0861
PubMed:View item in PubMed

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