Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells

Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchab...

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Bibliographic Details
Published in:PloS one 2013-03, Vol.8 (3), p.e57559
Main Authors: Lizunov, Vladimir A, Stenkula, Karin, Troy, Aaron, Cushman, Samuel W, Zimmerberg, Joshua
Format: Article
Language:English
Subjects:
Adipocytes - cytology
Adipocytes - metabolism
Animals
Biology
Cell Membrane Structures - genetics
Cell Membrane Structures - metabolism
Cell membranes
Childrens health
Clusters
Collision dynamics
Confinement
Diabetes
Dispersion
Dissociation
Elongation
Endocrinology
Engineering
Exocytosis
Fluorescence
Glucose
Glucose - genetics
Glucose - metabolism
Glucose transporter
Glucose Transporter Type 4 - genetics
Glucose Transporter Type 4 - metabolism
Homeostasis
Homeostasis - physiology
Insulin
Insulin - metabolism
Kidney diseases
Lipids
Localization
Male
Metabolism
Metabolites
Microscopy
Monomers
Physiological aspects
Protein Transport - physiology
Proteins
Rats
Rats, Sprague-Dawley
Regulation
Transporter
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Summary:Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0057559