Abstract:
OBJECTIVE:Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady-state recycling and subsequent re-internalization of GLUT4 on an insulin bolus. RESEARCH DESIGN AND METHODS:A confocal imaging technique was used in GLUT4-enhanced green fluorescent protein-transfected superficial muscle fibers in living mice. RESULTS:During the first 30 min of insulin stimulation, very few superficially or deeply located GLUT4 storage vesicles (>1 microm) moved in toto. Rather, big vesicles were stationary in their original position at sarcolemma or t-tubules and were locally depleted of GLUT4 by budding off of smaller vesicles. Photobleaching experiments revealed that during initial translocation and steady-state recycling, GLUT4 microvesicles (<1 microm) move from perinuclear GLUT4 depots out along the plasma membrane. Furthermore, after photobleaching of t-tubule areas, recovery of GLUT4 was slow or absent, indicating no recycling of GLUT4 from perinuclear or adjacent (1 microm) or more distant (20 microm) t-tubule areas. During waning of insulin effect, GLUT4 was re-internalized to basal stores with a delay in t-tubules compared with sarcolemma, probably reflecting delayed disappearance of insulin from t-tubules. CONCLUSIONS:In skeletal muscle, insulin reversibly stimulates local depletion of GLUT4 storage vesicles at sarcolemma and t-tubules rather than inducing movement of intact storage vesicles. During steady-state stimulation, recycling of GLUT4-containing microvesicles over longer distances (10-20 microm) takes place between perinuclear depots and sarcolemma but not at t-tubules.
journal_name
Diabetesjournal_title
Diabetesauthors
Lauritzen HP,Galbo H,Brandauer J,Goodyear LJ,Ploug Tdoi
10.2337/db06-1578subject
Has Abstractpub_date
2008-02-01 00:00:00pages
315-24issue
2eissn
0012-1797issn
1939-327Xpii
db06-1578journal_volume
57pub_type
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