Article

Selective Angiotensin II Receptor Antagonism Reduces Insulin Resistance in Obese Zucker Rats

Bristol-Myers Squibb, New York, New York, United States
Hypertension (Impact Factor: 7.63). 10/2001; 38(4):884-90. DOI: 10.1161/hy1101.092970
Source: PubMed

ABSTRACT Effects of oral administration of the angiotensin II receptor antagonist (selective AT(1)-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 (AT(1)-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.

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    • "In addition, other ACEi (temocapril) were demonstrated to improve insulin resistance and glucose intolerance through increasing glucose uptake, especially in skeletal muscle, at least in part through enhancement of the bradykinin-nitric oxide (NO) system and consequently glucose transporter-4 (GLUT-4) translocation [104]. Moreover, oral administration of irbesartan, 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 [46]. "
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    Peptides 07/2014; DOI:10.1016/j.peptides.2014.07.002 · 2.61 Impact Factor
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    Peptides 07/2014; DOI:10.1016/j.peptides.2014.04.021 · 2.61 Impact Factor
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    • "However, insulin levels both before and during ivgtt were lower in the losartan-treated rats than in the rats not treated with losartan and subjected for 35 days to sham gas exchanges. This suggests that losartan improved insulin sensitivity, as it did in the obese Zucker rats (Henriksen et al., 2001). Importantly, angiotensin II antagonism can improve glucose disposal by modulating insulin receptor/insulin receptor substrate-1 signaling in skeletal muscles , with a convergent action on some of the same intracellular mechanisms that are also beneficially affected by exercise training (Henriksen, 2007). "
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