Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats

Erik J Henriksen, Stephan Jacob, Tyson R. Kinnick, Mary K. Teachey, Michael Krekler

Research output: Contribution to journalArticle

254 Citations (Scopus)

Abstract

Effects of oral administration of the angiotensin II receptor antagonist (selective AT1-subtype) irbesartan on glucose tolerance and insulin action on skeletal-muscle glucose transport were assessed in the insulin-resistant obese Zucker rat. In the acute study, obese rats received either vehicle (water) or irbesartan 1 hour before the experiment. Although irbesartan had no effect on glucose transport (2-deoxyglucose uptake) in the epitrochlearis muscle, which consists mainly of type IIb fibers, acute angiotensin II receptor antagonism led to a dose-dependent increase in insulin action in the predominantly type I soleus muscle. Irbesartan at 25 and 50 mg/kg induced significant increases (41% and 50%, respectively; P<0.05) in insulin-mediated glucose transport. Moreover, these acute irbesartan-induced improvements in soleus-muscle glucose transport were associated with enhancements in whole-body insulin sensitivity (r=-0.732; P<0.05), as assessed during an oral glucose tolerance test. After chronic administration of irbesartan (21 days at 50 mg · kg-1 · d-1), glucose tolerance was enhanced further, and insulin-mediated glucose transport was significantly elevated in both epitrochlearis (32%) and soleus (73%) muscle. Chronic angiotensin II receptor antagonism was associated with significant increases in glucose transporter-4 (GLUT-4) protein expression in soleus (22%) and plantaris (20%) muscle and myocardium (15%). Chronic irbesartan-induced increases in whole-body insulin sensitivity were associated with increased insulin-mediated glucose transport in both epitrochlearis (r=-0.677; P<0.05) and soleus (r=-0.892; P<0.05) muscle. In summary, angiotensin II receptor (AT1-subtype) antagonism, either acutely or chronically, improves glucose tolerance, at least in part because of an enhancement in skeletal-muscle glucose transport, and the effect of chronic angiotensin II receptor antagonism on type I skeletal-muscle glucose uptake is associated with an increase in GLUT-4 protein expression.

Original languageEnglish (US)
Pages (from-to)884-890
Number of pages7
JournalHypertension
Volume38
Issue number4
StatePublished - 2001

Fingerprint

irbesartan
Zucker Rats
Angiotensin Receptors
Insulin Resistance
Glucose
Skeletal Muscle
Insulin
Facilitative Glucose Transport Proteins
Angiotensin II Type 1 Receptor Blockers
Muscles
Deoxyglucose
Glucose Tolerance Test
Oral Administration
Myocardium
Proteins

Keywords

  • Glucose
  • Irbesartan
  • Muscle, skeletal
  • Rats, Zucker
  • Receptors, angiotensin
  • Transport, glucose

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Henriksen, E. J., Jacob, S., Kinnick, T. R., Teachey, M. K., & Krekler, M. (2001). Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats. Hypertension, 38(4), 884-890.

Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats. / Henriksen, Erik J; Jacob, Stephan; Kinnick, Tyson R.; Teachey, Mary K.; Krekler, Michael.

In: Hypertension, Vol. 38, No. 4, 2001, p. 884-890.

Research output: Contribution to journalArticle

Henriksen, EJ, Jacob, S, Kinnick, TR, Teachey, MK & Krekler, M 2001, 'Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats', Hypertension, vol. 38, no. 4, pp. 884-890.
Henriksen, Erik J ; Jacob, Stephan ; Kinnick, Tyson R. ; Teachey, Mary K. ; Krekler, Michael. / Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats. In: Hypertension. 2001 ; Vol. 38, No. 4. pp. 884-890.
@article{a70ec8dedf8a462482a2b1ac580ff289,
title = "Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats",
abstract = "Effects of oral administration of the angiotensin II receptor antagonist (selective AT1-subtype) irbesartan on glucose tolerance and insulin action on skeletal-muscle glucose transport were assessed in the insulin-resistant obese Zucker rat. In the acute study, obese rats received either vehicle (water) or irbesartan 1 hour before the experiment. Although irbesartan had no effect on glucose transport (2-deoxyglucose uptake) in the epitrochlearis muscle, which consists mainly of type IIb fibers, acute angiotensin II receptor antagonism led to a dose-dependent increase in insulin action in the predominantly type I soleus muscle. Irbesartan at 25 and 50 mg/kg induced significant increases (41{\%} and 50{\%}, respectively; P<0.05) in insulin-mediated glucose transport. Moreover, these acute irbesartan-induced improvements in soleus-muscle glucose transport were associated with enhancements in whole-body insulin sensitivity (r=-0.732; P<0.05), as assessed during an oral glucose tolerance test. After chronic administration of irbesartan (21 days at 50 mg · kg-1 · d-1), glucose tolerance was enhanced further, and insulin-mediated glucose transport was significantly elevated in both epitrochlearis (32{\%}) and soleus (73{\%}) muscle. Chronic angiotensin II receptor antagonism was associated with significant increases in glucose transporter-4 (GLUT-4) protein expression in soleus (22{\%}) and plantaris (20{\%}) muscle and myocardium (15{\%}). Chronic irbesartan-induced increases in whole-body insulin sensitivity were associated with increased insulin-mediated glucose transport in both epitrochlearis (r=-0.677; P<0.05) and soleus (r=-0.892; P<0.05) muscle. In summary, angiotensin II receptor (AT1-subtype) antagonism, either acutely or chronically, improves glucose tolerance, at least in part because of an enhancement in skeletal-muscle glucose transport, and the effect of chronic angiotensin II receptor antagonism on type I skeletal-muscle glucose uptake is associated with an increase in GLUT-4 protein expression.",
keywords = "Glucose, Irbesartan, Muscle, skeletal, Rats, Zucker, Receptors, angiotensin, Transport, glucose",
author = "Henriksen, {Erik J} and Stephan Jacob and Kinnick, {Tyson R.} and Teachey, {Mary K.} and Michael Krekler",
year = "2001",
language = "English (US)",
volume = "38",
pages = "884--890",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats

AU - Henriksen, Erik J

AU - Jacob, Stephan

AU - Kinnick, Tyson R.

AU - Teachey, Mary K.

AU - Krekler, Michael

PY - 2001

Y1 - 2001

N2 - Effects of oral administration of the angiotensin II receptor antagonist (selective AT1-subtype) irbesartan on glucose tolerance and insulin action on skeletal-muscle glucose transport were assessed in the insulin-resistant obese Zucker rat. In the acute study, obese rats received either vehicle (water) or irbesartan 1 hour before the experiment. Although irbesartan had no effect on glucose transport (2-deoxyglucose uptake) in the epitrochlearis muscle, which consists mainly of type IIb fibers, acute angiotensin II receptor antagonism led to a dose-dependent increase in insulin action in the predominantly type I soleus muscle. Irbesartan at 25 and 50 mg/kg induced significant increases (41% and 50%, respectively; P<0.05) in insulin-mediated glucose transport. Moreover, these acute irbesartan-induced improvements in soleus-muscle glucose transport were associated with enhancements in whole-body insulin sensitivity (r=-0.732; P<0.05), as assessed during an oral glucose tolerance test. After chronic administration of irbesartan (21 days at 50 mg · kg-1 · d-1), glucose tolerance was enhanced further, and insulin-mediated glucose transport was significantly elevated in both epitrochlearis (32%) and soleus (73%) muscle. Chronic angiotensin II receptor antagonism was associated with significant increases in glucose transporter-4 (GLUT-4) protein expression in soleus (22%) and plantaris (20%) muscle and myocardium (15%). Chronic irbesartan-induced increases in whole-body insulin sensitivity were associated with increased insulin-mediated glucose transport in both epitrochlearis (r=-0.677; P<0.05) and soleus (r=-0.892; P<0.05) muscle. In summary, angiotensin II receptor (AT1-subtype) antagonism, either acutely or chronically, improves glucose tolerance, at least in part because of an enhancement in skeletal-muscle glucose transport, and the effect of chronic angiotensin II receptor antagonism on type I skeletal-muscle glucose uptake is associated with an increase in GLUT-4 protein expression.

AB - Effects of oral administration of the angiotensin II receptor antagonist (selective AT1-subtype) irbesartan on glucose tolerance and insulin action on skeletal-muscle glucose transport were assessed in the insulin-resistant obese Zucker rat. In the acute study, obese rats received either vehicle (water) or irbesartan 1 hour before the experiment. Although irbesartan had no effect on glucose transport (2-deoxyglucose uptake) in the epitrochlearis muscle, which consists mainly of type IIb fibers, acute angiotensin II receptor antagonism led to a dose-dependent increase in insulin action in the predominantly type I soleus muscle. Irbesartan at 25 and 50 mg/kg induced significant increases (41% and 50%, respectively; P<0.05) in insulin-mediated glucose transport. Moreover, these acute irbesartan-induced improvements in soleus-muscle glucose transport were associated with enhancements in whole-body insulin sensitivity (r=-0.732; P<0.05), as assessed during an oral glucose tolerance test. After chronic administration of irbesartan (21 days at 50 mg · kg-1 · d-1), glucose tolerance was enhanced further, and insulin-mediated glucose transport was significantly elevated in both epitrochlearis (32%) and soleus (73%) muscle. Chronic angiotensin II receptor antagonism was associated with significant increases in glucose transporter-4 (GLUT-4) protein expression in soleus (22%) and plantaris (20%) muscle and myocardium (15%). Chronic irbesartan-induced increases in whole-body insulin sensitivity were associated with increased insulin-mediated glucose transport in both epitrochlearis (r=-0.677; P<0.05) and soleus (r=-0.892; P<0.05) muscle. In summary, angiotensin II receptor (AT1-subtype) antagonism, either acutely or chronically, improves glucose tolerance, at least in part because of an enhancement in skeletal-muscle glucose transport, and the effect of chronic angiotensin II receptor antagonism on type I skeletal-muscle glucose uptake is associated with an increase in GLUT-4 protein expression.

KW - Glucose

KW - Irbesartan

KW - Muscle, skeletal

KW - Rats, Zucker

KW - Receptors, angiotensin

KW - Transport, glucose

UR - http://www.scopus.com/inward/record.url?scp=0035724736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035724736&partnerID=8YFLogxK

M3 - Article

VL - 38

SP - 884

EP - 890

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 4

ER -