Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells
(2013) In Diabetes 62(9). p.3114-3119- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4025596
- author
- Lizunov, Vladimir A. ; Lee, Jo-Ping ; Skarulis, Monica C. ; Zimmerberg, Joshua ; Cushman, Samuel W. and Stenkula, Karin LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 62
- issue
- 9
- pages
- 3114 - 3119
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- wos:000323421000018
- scopus:84887363321
- pmid:23801575
- ISSN
- 1939-327X
- DOI
- 10.2337/db12-1741
- language
- English
- LU publication?
- yes
- id
- 07475eec-0bf4-4be2-9acb-c330e8752e83 (old id 4025596)
- date added to LUP
- 2016-04-01 13:28:17
- date last changed
- 2022-03-29 07:36:22
@article{07475eec-0bf4-4be2-9acb-c330e8752e83,
abstract = {{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.}},
author = {{Lizunov, Vladimir A. and Lee, Jo-Ping and Skarulis, Monica C. and Zimmerberg, Joshua and Cushman, Samuel W. and Stenkula, Karin}},
issn = {{1939-327X}},
language = {{eng}},
number = {{9}},
pages = {{3114--3119}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells}},
url = {{http://dx.doi.org/10.2337/db12-1741}},
doi = {{10.2337/db12-1741}},
volume = {{62}},
year = {{2013}},
}