Molecular mechanism of angiotensin II-induced insulin resistance in aortic vascular smooth muscle cells: Roles of Protein Tyrosine Phosphatase-1B

Ketsawatsomkron, Pimonrat; Stepp, David W.; Fulton, David; Marrero, Mario B.

doi:10.1016/j.vph.2010.06.001

Cited by 13 publications

(9 citation statements)

References 44 publications

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“…AngII intracellular signaling involves both calcium and diacylglycerol generation that is consistent with downstream activation of conventional and novel PKC isoforms [22]. AngII is known to induce vascular insulin resistance in a PKC-dependent manner [24]. Our data demonstrated that both Capto and RBX independently conferred vascular benefits.…”

Section: Discussionsupporting

confidence: 61%

Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats

Bean

Kassab

et al. 2011

Cardiovasc Diabetol

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ObjectiveInsulin resistance, diabetes, and hypertension are considered elements of metabolic syndrome which is associated with vascular dysfunction. We investigated whether inhibition of protein kinase C (PKC) would affect vascular function in diabetic hypertensive (DH) rats.MethodsA combination of type 2 diabetes and arterial hypertension was produced in male Sprague Dawley rats by intrauterine protein deprivation (IUPD) followed by high salt diet. At the age of 32 weeks, DH rats were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril (Capto, 30 mg/kg), PKC inhibitor ruboxistaurin (RBX, 50 mg/kg) or vehicle (n = 8 per group) and blood pressure was monitored using telemetry. At the end of experiments, femoral arteries were dissected, and vascular reactivity was evaluated with isovolumic myography.ResultsThe IUPD followed by high salt diet resulted in significant elevation of plasma glucose, plasma insulin, and blood pressure. Endothelium-dependent vascular relaxation in response to acetylcholine was blunted while vascular contraction in response to phenylephrine was enhanced in the DH rats. Neither Capto nor RBX restored endothelium-dependent vascular relaxation while both suppressed vascular contraction. Ex-vivo incubation of femoral arteries from control rats with insulin induced dose-response vasorelaxation while insulin failed to induce vasorelaxation in the DH rat arteries. In the control arteries treated with endothelial nitric oxide synthase inhibitor L-NAME, insulin induced vasoconstriction that was exacerbated in DH rats. Capto and RBX partially inhibited insulin-stimulated vascular contraction.ConclusionThese findings suggest that PKC inhibition ameliorates functional endothelial insulin resistance and smooth muscle cell hypersensitivity to insulin, but does not restore acetylcholine-activated endothelium-dependent vasodilation in DH rats.

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Section: Discussionsupporting

confidence: 61%

Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats

Bean

Kassab

et al. 2011

Cardiovasc Diabetol

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“…Interestingly, it has recently been observed that ANG II increases PTP-1b expressionin vascular smooth muscle cells [71]. Such observations support the hypothesis that elevated ANG II levels acts to blunt leptin signalling and contribute to leptin resistance and obesity through enhancing PTP1b activity (see Fig.…”

Section: Influence Of Angiotensin Onleptin Signallingsupporting

confidence: 66%

The Role of Angiotensin in Obesity and Metabolic Disease

Mathai

Chen²,

Cornall³

et al. 2011

EMIDDT

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Obesity is associated with increased body fat composition and elevated risk of metabolic and cardiovascular disease. The activity of the renin-angiotensin system is generally increased in obesity and experimental evidence has shown that angiotensin influences appetite and metabolism as well as mechanisms that induce adipose tissue growth and metabolism in peripheral organs. This review summarises some of the key evidence from animal and human experiments that links the renin-angiotensin system to obesity and metabolic disease. This research has been greatly aided by the continuing development of new pharmaceuticals that inhibit the renin-angiotensin system. While their primary use is in the treatment of hypertension and heart failure, a range of experimental and clinical evidence indicates their potential use in the treatment of obesity and metabolic disease.

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“…Recent work by our group and others implicate inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) with subsequent elevations in angiotensin (Ang) II and aldosterone to alterations in insulin signaling pathways, reactive oxygen species formation and endothelial dysfunction in heart and kidney disease (Manhiani, 2012; Shephard 1999; Whaley-Connell 2011; Sherajee 2012; Hitomi 2011; Wei 2007; Ketsawatsomkaron 2010). Furthermore, all of the above features of insulin resistance correlate well with proteinuria in kidney disease and diastolic dysfunction in the heart, thereby, suggesting a critical role for insulin resistance/hyperinsulinemia as a potential unifying mechanism in the cardiorenal metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Resistance to insulin and kidney disease in the cardiorenal metabolic syndrome; role for angiotensin II

Nistala

Whaley‐Connell

2013

Molecular and Cellular Endocrinology

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The presence of insulin resistance is increasingly recognized as an important contributor to early stage kidney disease independent of the contribution of diabetes. Important in this relationship is the strong correlation between hyperinsulinemia and low levels of albuminuria (e.g microalbuminuria). Recent work highlight mechanisms for glomerular/tubulointerstitial injury with excess insulin and emerging evidence identifies a unique role for insulin metabolic signaling and altered handling of salt reabsorption at the level of the proximal tubule. Evidence is also emerging for the role of insulin signaling in the glomerulus both epithelial and endothelial. Central to the mechanism of injury is inappropriate activation of the RAAS.

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Molecular mechanism of angiotensin II-induced insulin resistance in aortic vascular smooth muscle cells: Roles of Protein Tyrosine Phosphatase-1B

Cited by 13 publications

References 44 publications

Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats

Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats

The Role of Angiotensin in Obesity and Metabolic Disease

Resistance to insulin and kidney disease in the cardiorenal metabolic syndrome; role for angiotensin II

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