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

24 Citations (Scopus)

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

Fingerprint

Insulin-Like Growth Factor I
Insulin
Glucose
Brain
Proteins
GTP Phosphohydrolases
Mitogen-Activated Protein Kinase Kinases
Protein C
Hypoglycemia
Astrocytes
Cell Membrane
Peptides

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Fernandez, A. M., Hernandez-Garzón, E., Perez-Domper, P., Perez-Alvarez, A., Mederos, S., Matsui, T., ... 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

Insulin regulates astrocytic glucose handling through cooperation with IGF-I. / Fernandez, Ana M.; Hernandez-Garzón, Edwin; Perez-Domper, Paloma; Perez-Alvarez, Alberto; Mederos, Sara; Matsui, Takashi; Santi, Andrea; Trueba-Saiz, Angel; García-Guerra, Lucía; Pose-Utrilla, Julia; Fielitz, Jens; Olson, Eric N.; De La Rosa, Ruben Fernandez; Garcia, Luis Garcia; Pozo, Miguel Angel; Iglesias, Teresa; Araque, Alfonso; Soya, Hideaki; Perea, Gertrudis; Martin, Eduardo D.; Aleman, Ignacio Torres.

In: Diabetes, Vol. 66, No. 1, 01.01.2017, p. 64-74.

Research output: Contribution to journalArticle

Fernandez, AM, 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, EN, De La Rosa, RF, Garcia, LG, Pozo, MA, Iglesias, T, Araque, A, Soya, H, Perea, G, Martin, ED & Aleman, IT 2017, 'Insulin regulates astrocytic glucose handling through cooperation with IGF-I', Diabetes, vol. 66, no. 1, pp. 64-74. https://doi.org/10.2337/db16-0861
Fernandez AM, Hernandez-Garzón E, Perez-Domper P, Perez-Alvarez A, Mederos S, Matsui T et al. Insulin regulates astrocytic glucose handling through cooperation with IGF-I. Diabetes. 2017 Jan 1;66(1):64-74. https://doi.org/10.2337/db16-0861
Fernandez, Ana M. ; Hernandez-Garzón, Edwin ; Perez-Domper, Paloma ; Perez-Alvarez, Alberto ; Mederos, Sara ; Matsui, Takashi ; Santi, Andrea ; Trueba-Saiz, Angel ; García-Guerra, Lucía ; Pose-Utrilla, Julia ; Fielitz, Jens ; Olson, Eric N. ; De La Rosa, Ruben Fernandez ; Garcia, Luis Garcia ; Pozo, Miguel Angel ; Iglesias, Teresa ; Araque, Alfonso ; Soya, Hideaki ; Perea, Gertrudis ; Martin, Eduardo D. ; Aleman, Ignacio Torres. / Insulin regulates astrocytic glucose handling through cooperation with IGF-I. In: Diabetes. 2017 ; Vol. 66, No. 1. pp. 64-74.
@article{4a5225d732c94eb1b0d20b945956a086,
title = "Insulin regulates astrocytic glucose handling through cooperation with IGF-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.",
author = "Fernandez, {Ana M.} and Edwin Hernandez-Garz{\'o}n and Paloma Perez-Domper and Alberto Perez-Alvarez and Sara Mederos and Takashi Matsui and Andrea Santi and Angel Trueba-Saiz and Luc{\'i}a Garc{\'i}a-Guerra and Julia Pose-Utrilla and Jens Fielitz and Olson, {Eric N.} and {De La Rosa}, {Ruben Fernandez} and Garcia, {Luis Garcia} and Pozo, {Miguel Angel} and Teresa Iglesias and Alfonso Araque and Hideaki Soya and Gertrudis Perea and Martin, {Eduardo D.} and Aleman, {Ignacio Torres}",
year = "2017",
month = "1",
day = "1",
doi = "10.2337/db16-0861",
language = "English (US)",
volume = "66",
pages = "64--74",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "1",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85007393308&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85007393308&partnerID=8YFLogxK

U2 - 10.2337/db16-0861

DO - 10.2337/db16-0861

M3 - Article

C2 - 27999108

AN - SCOPUS:85007393308

VL - 66

SP - 64

EP - 74

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -