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- Title
Large GLUT4 Vesicles Are Stationary While Locally and Reversibly Depleted During Transient Insulin Stimulation of Skeletal Muscle of Living Mice.
- Authors
Lauritzen, Hans P. M. M.; Galbo, Henrik; Brandauer, Josef; Goodyear, Laurie J.; Ploug, Thorkil
- 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 rain of insulin stimulation, very few superficially or deeply located GLUT4 storage vesicles (> 1 µm) 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 µm) 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 µm) or more distant (20 µm) 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 GLUT4containing microvesicles over longer distances (10-20 µm) takes place between perinuclear depots and sarcolemma but not at t-tubules. Diabetes 57:315-324, 2008
- Subjects
INSULIN; GLUCOSE; LABORATORY mice; CELL membranes; SARCOLEMMA
- Publication
Diabetes, 2008, Vol 57, Issue 2, p315
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-1578