TY - JOUR
T1 - Insulin regulates astrocytic glucose handling through cooperation with IGF-I
AU - Fernandez, Ana M.
AU - Hernandez-Garzón, Edwin
AU - Perez-Domper, Paloma
AU - Perez-Alvarez, Alberto
AU - Mederos, Sara
AU - Matsui, Takashi
AU - Santi, Andrea
AU - Trueba-Saiz, Angel
AU - García-Guerra, Lucía
AU - Pose-Utrilla, Julia
AU - Fielitz, Jens
AU - Olson, Eric N.
AU - De La Rosa, Ruben Fernandez
AU - Garcia, Luis Garcia
AU - Pozo, Miguel Angel
AU - Iglesias, Teresa
AU - Araque, Alfonso
AU - Soya, Hideaki
AU - Perea, Gertrudis
AU - Martin, Eduardo D.
AU - Aleman, Ignacio Torres
N1 - Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db16-0861
DO - 10.2337/db16-0861
M3 - Article
C2 - 27999108
AN - SCOPUS:85007393308
SN - 0012-1797
VL - 66
SP - 64
EP - 74
JO - Diabetes
JF - Diabetes
IS - 1
ER -
