Angiotensin II decreases glucose uptake by downregulation of GLUT1 in the cell membrane of the vascular smooth muscle cell line A10.
Recent evidence suggests a crosstalk between angiotensin II (Ang II) and insulin. However, whether this crosstalk affects glucose uptake, particularly in terms of actin filament involvement, has not yet been studied in vascular smooth muscle cells. Pretreatment of cells with either Ang II or cytochalasin D disarranged actin filaments in a time-dependent manner and inhibited glucose uptake. However, insulin increased actin reorganization and glucose uptake. Membrane fractionation studies showed that Ang II decreased GLUT-1 at the cell membrane, whereas it increased GLUT-1 in the cytoplasm, indicating that Ang II may cause internalization of GLUT-1 via actin disorganization, consequently decreasing glucose uptake. The effects of Ang II on glucose uptake and actin reorganization were blocked by AT1 receptor antagonist, but not by AT2 antagonist. Either P38 or ERK1/2 inhibitors partially reversed the Ang II-inhibited actin reorganization and glucose uptake, suggesting that MAPK signaling pathways could be involved as downstream events in Ang II signaling, and this signaling may interfere with insulin-induced actin reorganization and glucose uptake. These data imply that Ang II induces insulin resistance by decreasing glucose uptake via disarrangement of actin filaments, which provides a novel insight into understanding of insulin resistance by Ang II at the molecular level.
Masori
Maria
M
Department of Nutrition, Division of Nutrition and Metabolism, Graduate School of Medicine, University of Tokushima, Tokushima, Japan.
Hamamoto
Akiko
A
Mawatari
Kazuaki
K
Harada
Nagakatu
N
Takahasi
Akira
A
Nakaya
Yutaka
Y
D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane; D015638:Cytochalasin D / Q000494:pharmacology; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D000199:Actins; D051272:Glucose Transporter Type 1; D007328:Insulin; D000804:Angiotensin II; D015638:Cytochalasin D; D005947:Glucose