Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

被引：81

作者：

Fernandez, Ana M. ^{[1
,2
]}

Hernandez-Garzon, Edwin ^{[1
,2
]}

Perez-Domper, Paloma ^{[1
,2
]}

Perez-Alvarez, Alberto ^{[1
,3
]}

Mederos, Sara ^{[1
]}

Matsui, Takashi ^{[4
]}

Santi, Andrea ^{[1
,2
]}

Trueba-Saiz, Angel ^{[1
,2
]}

Garcia-Guerra, Lucia ^{[2
,5
]}

Pose-Utrilla, Julia ^{[2
,5
]}

Fielitz, Jens ^{[6
,7
,8
]}

Olson, Eric N. ^{[9
]}

Fernandez de la Rosa, Ruben ^{[10
]}

Garcia Garcia, Luis ^{[10
]}

Angel Pozo, Miguel ^{[10
]}

Iglesias, Teresa ^{[2
,5
]}

Araque, Alfonso ^{[1
]}

Soya, Hideaki ^{[4
]}

Perea, Gertrudis ^{[1
]}

Martin, Eduardo D. ^{[11
]}

Torres Aleman, Ignacio ^{[1
,2
]}

机构：

[1] CSIC, Cajal Inst, Madrid, Spain

[2] CIBERNED, Madrid, Spain

[3] Ctr Mol Neurobiol Hamburg, Hamburg, Germany

[4] Univ Tsukuba, Lab Exercise Biochem & Neuroendocrinol, Tsukuba, Ibaraki, Japan

[5] Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain

[6] Charite, Max Delbruck Ctr Mol Med, Expt & Clin Res Ctr, Berlin, Germany

[7] Brandenburg Heart Ctr, Brandenburg, Germany

[8] Med Univ Brandenburg, Brandenburg, Germany

[9] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA

[10] Univ Complutense Madrid, Pluridisciplinary Inst, Madrid, Spain

[11] Univ Castilla La Mancha, Inst Res Neurol Disabil, Sci & Technol Pk, Albacete, Spain

来源：

DIABETES | 2017年 / 66卷 / 01期

关键词：

GROWTH-FACTOR-I; BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; RECEPTOR; PROTEIN; EXPRESSION; TRANSPORT; METABOLISM; GLUT1;

D O I：

10.2337/db16-0861

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：64 / 74

页数：11

共 51 条

[1] THE BINDING OF INSULIN TO CEREBRAL CAPILLARIES AND ASTROCYTES OF THE RAT [J].