1. Insulin regulates astrocytic glucose handling through cooperation with IGF-I
- Author
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Alberto Perez-Alvarez, Ignacio Torres Aleman, Edwin Hernández-Garzón, Luis Garcia Garcia, Takashi Matsui, Gertrudis Perea, Lucía García-Guerra, Angel Trueba-Saiz, Rubén Fernández de la Rosa, Paloma Pérez-Domper, Jens Fielitz, Teresa Iglesias, Alfonso Araque, Julia Pose-Utrilla, Eduardo D. Martín, Eric N. Olson, Sara Mederos, Ana M. Fernandez, Andrea Santi, Hideaki Soya, Miguel A. Pozo, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), and European Commission
- Subjects
Male ,0301 basic medicine ,Scaffold protein ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,RAC1 ,Carbohydrate metabolism ,Polymerase Chain Reaction ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Insulin ,Lactic Acid ,Insulin-Like Growth Factor I ,Protein kinase A ,Immunoassay ,Neurons ,Glucose Transporter Type 1 ,biology ,Glycogen ,Biological Transport ,Glucose ,030104 developmental biology ,Endocrinology ,chemistry ,Astrocytes ,Positron-Emission Tomography ,biology.protein ,GLUT1 ,030217 neurology & neurosurgery ,Plasmids - 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., This work was funded by MINECO (Spain) grants SAF2010-60051 and SAF2013-40710-R, and by CIBERNED. E.H.-G. was partially funded by a fellowship from ColFuturo and CIBERNED. T.I. is funded by MINECO (SAF2014-52737-P). T.I. and I.T.A. are funded by CIBERNED and Comunidad de Madrid, Spain (P2010/BMD-2331-Neurodegmodels).
- Published
- 2017