GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta

James L. Park, Robert D. Loberg, Damon Duquaine, Hongyu Zhang, Baljit K. Deo, Noelia Ardanaz, Jami Coyle, Kevin B. Atkins, Marylee Schin, Maureen J. Charron, Arno K. Kumagai, Patrick J. Pagano, Frank C. Brosius

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective - We hypothesized that GLUT4 is a predominant facultative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction. Methods and Results - Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4 and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, ≈50% of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F-mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46% decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT-mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4. Conclusions - Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension.

Original languageEnglish (US)
Pages (from-to)1596-1602
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume25
Issue number8
DOIs
StatePublished - Aug 2005

Fingerprint

Facilitative Glucose Transport Proteins
Indinavir
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Aorta
Muscle Contraction
Glucose
Serotonin
Serotonin Plasma Membrane Transport Proteins
Wild Animals
Dinoprost
Vascular Diseases
Angiotensin II
Endothelium
Norepinephrine
Arteries
Hypertension

Keywords

  • Glucose
  • GLUT4
  • Indinavir
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta. / Park, James L.; Loberg, Robert D.; Duquaine, Damon; Zhang, Hongyu; Deo, Baljit K.; Ardanaz, Noelia; Coyle, Jami; Atkins, Kevin B.; Schin, Marylee; Charron, Maureen J.; Kumagai, Arno K.; Pagano, Patrick J.; Brosius, Frank C.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 25, No. 8, 08.2005, p. 1596-1602.

Research output: Contribution to journalArticle

Park, JL, Loberg, RD, Duquaine, D, Zhang, H, Deo, BK, Ardanaz, N, Coyle, J, Atkins, KB, Schin, M, Charron, MJ, Kumagai, AK, Pagano, PJ & Brosius, FC 2005, 'GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 8, pp. 1596-1602. https://doi.org/10.1161/01.ATV.0000170137.41079.ab
Park, James L. ; Loberg, Robert D. ; Duquaine, Damon ; Zhang, Hongyu ; Deo, Baljit K. ; Ardanaz, Noelia ; Coyle, Jami ; Atkins, Kevin B. ; Schin, Marylee ; Charron, Maureen J. ; Kumagai, Arno K. ; Pagano, Patrick J. ; Brosius, Frank C. / GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2005 ; Vol. 25, No. 8. pp. 1596-1602.
@article{41875ab982a84133bf92eeec37232c06,
title = "GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta",
abstract = "Objective - We hypothesized that GLUT4 is a predominant facultative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction. Methods and Results - Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4 and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, ≈50{\%} of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F2α-mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46{\%} decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT-mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4. Conclusions - Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension.",
keywords = "Glucose, GLUT4, Indinavir, Vascular smooth muscle",
author = "Park, {James L.} and Loberg, {Robert D.} and Damon Duquaine and Hongyu Zhang and Deo, {Baljit K.} and Noelia Ardanaz and Jami Coyle and Atkins, {Kevin B.} and Marylee Schin and Charron, {Maureen J.} and Kumagai, {Arno K.} and Pagano, {Patrick J.} and Brosius, {Frank C.}",
year = "2005",
month = "8",
doi = "10.1161/01.ATV.0000170137.41079.ab",
language = "English (US)",
volume = "25",
pages = "1596--1602",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta

AU - Park, James L.

AU - Loberg, Robert D.

AU - Duquaine, Damon

AU - Zhang, Hongyu

AU - Deo, Baljit K.

AU - Ardanaz, Noelia

AU - Coyle, Jami

AU - Atkins, Kevin B.

AU - Schin, Marylee

AU - Charron, Maureen J.

AU - Kumagai, Arno K.

AU - Pagano, Patrick J.

AU - Brosius, Frank C.

PY - 2005/8

Y1 - 2005/8

N2 - Objective - We hypothesized that GLUT4 is a predominant facultative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction. Methods and Results - Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4 and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, ≈50% of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F2α-mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46% decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT-mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4. Conclusions - Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension.

AB - Objective - We hypothesized that GLUT4 is a predominant facultative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction. Methods and Results - Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4 and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, ≈50% of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F2α-mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46% decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT-mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4. Conclusions - Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension.

KW - Glucose

KW - GLUT4

KW - Indinavir

KW - Vascular smooth muscle

UR - http://www.scopus.com/inward/record.url?scp=23244458309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23244458309&partnerID=8YFLogxK

U2 - 10.1161/01.ATV.0000170137.41079.ab

DO - 10.1161/01.ATV.0000170137.41079.ab

M3 - Article

C2 - 15890973

AN - SCOPUS:23244458309

VL - 25

SP - 1596

EP - 1602

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 8

ER -