Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells
Författare
Summary, in English
Systemic glucose homeostasis is profoundly influenced by adipose cell function. Here we investigated GLUT4 dynamics in living adipose cells from human subjects with varying BMI and insulin sensitivity index (S-i) values. Cells were transfected with hemagglutinin (HA)-GLUT4-green fluorescent protein (GFP)/mCherry (red fluorescence), and were imaged live using total internal reflection fluorescence and confocal microscopy. HA-GLUT4-GFP redistribution to the plasma membrane (PM) was quantified by surface-exposed HA epitope. In the basal state, GLUT4 storage vesicle (GSV) trafficking to and fusion with the PM were invariant with donor subject S-i, as was total cell-surface GLUT4. In cells from insulin-sensitive subjects, insulin augmented GSV tethering and fusion approximately threefold, resulting in a corresponding increase in total PM GLUT4. However, with decreasing S-i, these effects diminished progressively. All insulin-induced effects on GLUT4 redistribution and trafficking correlated strongly with S-i and only weakly with BMI. Thus, while basal GLUT4 dynamics and total cell-surface GLUT4 are intact in human adipose cells, independent of donor S-i, cells from insulin-resistant donors show markedly impaired GSV tethering and fusion responses to insulin, even after overnight culture. This altered insulin responsiveness is consistent with the hypothesis that adipose cellular dysfunction is a primary contributor to systemic metabolic dysfunction.
Avdelning/ar
- Medical Protein Science
- EXODIAB: Excellence of Diabetes Research in Sweden
Publiceringsår
2013
Språk
Engelska
Sidor
3114-3119
Publikation/Tidskrift/Serie
Diabetes
Volym
62
Issue
9
Dokumenttyp
Artikel i tidskrift
Förlag
American Diabetes Association Inc.
Ämne
- Endocrinology and Diabetes
Status
Published
Forskningsgrupp
- Medical Protein Science
ISBN/ISSN/Övrigt
- ISSN: 1939-327X