Angiotensin II-induced NADPH Oxidase Activation Impairs Insulin Signaling in Skeletal Muscle Cells

Wei, Yongzhong; Sowers, James R.; Nistala, Ravi; Gong, Heping; Uptergrove, Grace M.E.; Clark, Suzanne E.; Morris, E. Matthew; Szary, Nicholas M.; Manrique, Camila; Stump, Craig S.

doi:10.1074/jbc.m601320200

Cited by 262 publications

(245 citation statements)

References 60 publications

Supporting

Mentioning

226

Contrasting

Unclassified

Order By: Relevance

“…ROS production has been reported to be associated with reduced nitric oxide (NO) bioavailability through scavenging by superoxide anions (Wei et al 2006) and/or endothelial NO synthase uncoupling (Crabtree et al 2009). In the present study, we evaluated the instant mitochondrial ROS impregnation at two moments of the perfusion: just before ischemia and at the end of reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

View full text Add to dashboard Cite

Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10-or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H 2 O 2 release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H 2 O 2 when they oxidize FADH 2 -linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration AGE (2011) of the coronary perfusion was explained by an increased mitochondrial ROS release related to the preservation of complex II activity during reperfusion.

show abstract

Section: Discussionmentioning

confidence: 99%

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

View full text Add to dashboard Cite

show abstract

“…However, the total volumes of non-myocyte components are small in the soleus, and earlier studies using immunohistochemistry have shown that protein levels of MCP-1 and TNF-a were increased by 1.5-fold in myocytes. 33 Therefore, we speculate that the induction of the inflammatory cytokines in response to the Ang II infusion occurred mainly in myocytes.…”

Section: Discussionmentioning

confidence: 89%

Angiotensin II receptor activation in youth triggers persistent insulin resistance and hypertension—a legacy effect?

et al. 2011

View full text Add to dashboard Cite

Although the involvement of angiotensin II (Ang II) in insulin resistance and hypertension has been established, the temporal relationships between Ang II receptor activation and changes in insulin sensitivity and blood pressure are not clear. To better understand this issue, we infused rats with Ang II (200 ng kg À1 min À1 ) or vehicle for 4 weeks and assessed the residual effects after the discontinuation of the infusion on blood pressure, insulin sensitivity and tissue parameters of inflammation. Four weeks after the discontinuation of the Ang II infusion, the blood pressure was higher by 12.8 mm Hg, and insulin sensitivity as determined by a euglycemic hyperinsulinemic glucose clamp was reduced (glucose infusion rate: 11.1 ± 0.7 vs. 17.6±0.5 mg kg À1 min À1 ) in the Ang II-treated group compared with controls. The persistent hypertension and insulin resistance were associated with greater than two-fold increases in macrophage chemoattractant protein-1, tumor necrosis factor-a and thiobarbituric acid-reactive substrates in the soleus muscle. Furthermore, total and activated forms of Rac-1, a regulatory subunit of the NADPH oxidase complex, were increased by 144 ± 14% and 277 ± 82%, respectively, in the skeletal muscle of Ang II-treated rats. These residual effects after Ang II infusion were all attenuated by the co-administration of tempol, a free radical scavenger, or candesartan with Ang II. The effects of candesartan were not mimicked by hydralazine at an equidepressant dose. These findings suggest that Ang II receptor activation in youth triggers the upregulation of inflammatory cytokines and the production of reactive oxygen species, thereby inducing later insulin resistance and hypertension. INTRODUCTIONEvidence from patients and animal models has indicated that the angiotensin II (Ang II) type 1 receptor (AT 1 receptor) has a major role in the development of insulin resistance and hypertension. 1-4 However, the relationship between timing of the AT 1 receptor activation and the development (and persistence) of changes in insulin sensitivity and blood pressure has not been fully elucidated. Interestingly, the Trial of Preventing Hypertension Study showed that the treatment of prehypertensive patients with the AT 1 receptor blocker (ARB) candesartan for 2 years significantly delayed the progression from pre-hypertension to stage 1 hypertension during the following 2 years. 5 This finding suggests long-lasting effects of transitory activation of the AT 1 receptor in the development of hypertension. The results of the Trial of Preventing Hypertension Study bear certain similarities to those of a study by Holman et al. 6 (United Kingdom Prospective Diabetes Study), indicating the so-called 'legacy effect' . These authors found that the reduction of microvascular events continued for 10 years, in spite of the loss of differences in glycemic control after 10 years of intensive glycemic control had been discontinued. Furthermore, such 'legacy

show abstract

“…Aliskiren blocks the activation of RAS at the initial step of renin inhibition, and has been shown to improve glucose transport in the skeletal muscle tissue from renin transgenic rats (Lastra et al, 2009). Since Ang II is known to directly impair insulin signaling through NAD(P)H oxidase activation in skeletal muscle cells (Wei et al, 2006), aliskiren is considered to be an attractive therapeutic approach to ameliorate insulin resistance associated with HF. On the other hand, NEFA was increased in MI mice and was normalized by aliskiren, suggesting that HF-induced lipolysis of adipose tissue is alleviated by aliskiren.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the peripheral effects of insulin resistance are likely to represent a major metabolic feature of the pathophysiology of HF, contributing to key clinical symptoms such as breathlessness and early muscle fatigue (Kinugawa et al, 2015;Okita et al, 2013;Wilson et al, 1993). Multiple mechanisms of insulin resistance have already been identified, including increased oxidative stress and hyperactivation of the renin-angiotensin system (RAS) (Officers et al, 2002;Wei et al, 2006). We previously reported that insulin resistance was induced in experimental HF in mice (Ohta et al, 2011), and a later study showed that this induction was accompanied by increased local angiotensin II (Ang II) in the skeletal muscle and subsequent NAD(P)H oxidase-derived oxidative stress (Fukushima et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice

Fukushima

Kinugawa

Takada

et al. 2016

European Journal of Pharmacology

View full text Add to dashboard Cite

Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10 mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice.Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress.

show abstract

Angiotensin II-induced NADPH Oxidase Activation Impairs Insulin Signaling in Skeletal Muscle Cells

Cited by 262 publications

References 60 publications

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Angiotensin II receptor activation in youth triggers persistent insulin resistance and hypertension—a legacy effect?

Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice

Contact Info

Product

Resources

About