Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells

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Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells. / Lizunov, Vladimir A.; Lee, Jo-Ping; Skarulis, Monica C.; Zimmerberg, Joshua; Cushman, Samuel W.; Stenkula, Karin.

In: Diabetes, Vol. 62, No. 9, 2013, p. 3114-3119.

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Harvard

Lizunov, VA, Lee, J-P, Skarulis, MC, Zimmerberg, J, Cushman, SW & Stenkula, K 2013, 'Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells', Diabetes, vol. 62, no. 9, pp. 3114-3119. https://doi.org/10.2337/db12-1741

APA

Lizunov, V. A., Lee, J-P., Skarulis, M. C., Zimmerberg, J., Cushman, S. W., & Stenkula, K. (2013). Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells. Diabetes, 62(9), 3114-3119. https://doi.org/10.2337/db12-1741

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Author

Lizunov, Vladimir A. ; Lee, Jo-Ping ; Skarulis, Monica C. ; Zimmerberg, Joshua ; Cushman, Samuel W. ; Stenkula, Karin. / Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells. In: Diabetes. 2013 ; Vol. 62, No. 9. pp. 3114-3119.

RIS

TY - JOUR

T1 - Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells

AU - Lizunov, Vladimir A.

AU - Lee, Jo-Ping

AU - Skarulis, Monica C.

AU - Zimmerberg, Joshua

AU - Cushman, Samuel W.

AU - Stenkula, Karin

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.2337/db12-1741

DO - 10.2337/db12-1741

M3 - Article

VL - 62

SP - 3114

EP - 3119

JO - Diabetes

JF - Diabetes

SN - 1939-327X

IS - 9

ER -