The insulin-regulated aminopeptidase IRAP is colocalised with GLUT4 in the mouse hippocampus - potential role in modulation of glucose uptake in neurones?

It is proposed that insulin‐regulated aminopeptidase (IRAP) is the site of action of two peptides, angiotensin IV and LVV‐hemorphin 7, which have facilitatory effects on learning and memory. In fat and muscles, IRAP codistributes with the insulin‐responsive glucose transporter GLUT4 in specialised v...

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Published in:The European journal of neuroscience Vol. 28; no. 3; pp. 588 - 598
Main Authors: Fernando, Ruani N., Albiston, Anthony L., Chai, Siew Y.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01.08.2008
Subjects:
Angiotensin II - analogs & derivatives
Angiotensin II - metabolism
Animals
Cerebellum - cytology
Cerebellum - metabolism
Cystinyl Aminopeptidase - metabolism
Deoxyglucose - metabolism
Glucose - metabolism
Glucose Transport Proteins, Facilitative - metabolism
glucose transporter
Glucose Transporter Type 3 - metabolism
Glucose Transporter Type 4 - metabolism
Hemoglobins - metabolism
Hippocampus - cytology
Hippocampus - metabolism
Humans
Insulin - metabolism
Male
memory
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurons - cytology
Neurons - metabolism
Peptide Fragments - metabolism
ISSN:0953-816X, 1460-9568, 1460-9568
Online Access:Get full text
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Summary:It is proposed that insulin‐regulated aminopeptidase (IRAP) is the site of action of two peptides, angiotensin IV and LVV‐hemorphin 7, which have facilitatory effects on learning and memory. In fat and muscles, IRAP codistributes with the insulin‐responsive glucose transporter GLUT4 in specialised vesicles, where it plays a role in the tethering and/or trafficking of these vesicles. This study investigated whether an analogous system exists in two functionally distinct regions of the brain, the hippocampus and the cerebellum. In the hippocampus, IRAP was found in the pyramidal neurones where it exhibited a high degree of colocalisation with GLUT4. Consistent with the role of GLUT4 in insulin‐responsive tissues, the glucose transporter was thought to be responsible for facilitating glucose uptake into these pyramidal neurones in response to potassium‐induced depolarisation or cAMP activation as the glucose influx was sensitive to indinavir treatment. Angiotensin IV and LVV‐hemorphin 7 enhanced this activity‐dependent glucose uptake in hippocampal slices. In contrast, in the cerebellum, where the distribution of IRAP was dissociated from GLUT4, the effect of the peptides on glucose uptake was absent. We propose that the modulation of glucose uptake by angiotensin IV and LVV‐hemorphin 7 is region‐specific and is critically dependent on a high degree of colocalisation between IRAP and GLUT4. These findings also confirm a role for IRAP and GLUT4 in activity‐dependent glucose uptake in hippocampal neurones.
Bibliography:istex:1EF88E659618099A00AC189EBC0BE1C9FD7CB8F7
ark:/67375/WNG-1H7JTCCH-8
ArticleID:EJN6347
ObjectType-Article-2
SourceType-Scholarly Journals-1
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ISSN:0953-816X
1460-9568
1460-9568
DOI:10.1111/j.1460-9568.2008.06347.x