2024-03-28T09:43:43Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1878292022-09-23T10:20:21Zcom_10261_22com_10261_1com_10261_54col_10261_275col_10261_307
Insulin regulates astrocytic glucose handling through cooperation with IGF-I
Fernández García, Ana María
Hernandez-Garzón, Edwin
Pérez-Domper, Paloma
Pérez-Álvarez, Alberto
Mederos, Sara
Matsui, Takashi
Santi, Andrea
Trueba Saiz, Ángel
García-Guerra, Lucía
Pose-Utrilla, Julia
Fielitz, Jens
Olson, Eric N.
Fernandez de la Rosa, Ruben
Garcia Garcia, Luis
Pozo, Miguel Angel
Iglesias, Teresa
Araque, Alfonso
Soya, Hideaki
Perea, Gertrudis
Martín, Eduardo D.
Torres Alemán, Ignacio
Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
Comunidad de Madrid
Ministerio de Ciencia e Innovación (España)
European Commission
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).
Peer reviewed
2019-08-07T12:38:21Z
2019-08-07T12:38:21Z
2017
artículo
http://purl.org/coar/resource_type/c_6501
Diabetes 66(1): 64-74 (2017)
0012-1797
http://hdl.handle.net/10261/187829
10.2337/db16-0861
1939-327X
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100004587
27999108
en
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-40710-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-52737-P
S2010/BMD-2331/Neurodegmodels
https://doi.org/10.2337/db16-0861
Sí
none
American Diabetes Association