Journal
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 81
Volume 81, Issue -, Pages 507-532Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-biochem-060109-094246
Keywords
GLUT4; insulin signaling; vesicle trafficking; metabolic syndrome; Golgi matrix
Categories
Funding
- NIDDK NIH HHS [R01 DK075772, DK075772] Funding Source: Medline
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To enhance glucose uptake into muscle and fat cells, insulin stimulates the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface. This response requires the intersection of insulin signaling and vesicle trafficking pathways, and it is compromised in the setting of overnutrition to cause insulin resistance. Insulin signals through AS160/Tbc1D4 and Tbc1D1 to modulate Rab GTPases and through the Rho GTPase TC10 alpha to act on other targets. In unstimulated cells, GLUT4 is incorporated into specialized storage vesicles containing IRAP, LRP1, sortilin, and VAMP2, which are sequestered by TUG, Ubc9, and other proteins. Insulin mobilizes these vesicles directly to the plasma membrane, and it modulates the trafficking itinerary so that cargo recycles from endosomes during ongoing insulin exposure. Knowledge of how signaling and trafficking pathways are coordinated will be essential to understanding the pathogenesis of diabetes and the metabolic syndrome and may also inform a wide range of other physiologies.
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