ArticleCanadian journal of physiology and pharmacology2008
Impaired insulin-mediated vasorelaxation in a nonobese model of type 2 diabetes: role of endothelin-1.
Article in Canadian journal of physiology and pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- USP33 alleviates FIS1-dependent mitochondrial fission and cardiac microvascular injury in diabetic cardiomyopathy via deubiquitinating and stabilizing ATG7.Cell death & disease · 2026Article
- Skeletal muscle microvascular hemodynamic responses during hyperinsulinemic-euglycemic clamp in a Zucker Diabetic Sprague Dawley rat model of type 2 diabetes.Frontiers in physiology · 2025Article
- The role of fibrinolysis in the development of prediabetes-associated coronary heart disease: a focus on the plasminogen activator inhibitor -1 and its potential use as a predictive marker in diet-induced prediabetes.Frontiers in nutrition · 2023Article
- Plasma Brain Natriuretic Peptide, Endothelin-1, and Matrix Metalloproteinase 9 Expression and Significance in Type 2 Diabetes Mellitus Patients with Ischemic Heart Disease.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
- Cerebrovasculoprotective effects of azilsartan medoxomil in diabetes.Translational research : the journal of laboratory and clinical medicine · 2014Article
- Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes.American journal of physiology. Heart and circulatory physiology · 2013Article
- Cerebral myogenic reactivity and blood flow in type 2 diabetic rats: role of peroxynitrite in hypoxia-mediated loss of myogenic tone.The Journal of pharmacology and experimental therapeutics · 2012Article
- Internal pudendal artery from type 2 diabetic female rats demonstrate elevated endothelin-1-mediated constriction.The journal of sexual medicine · 2011Article
- Daily physical activity enhances reactivity to insulin in skeletal muscle arterioles of hyperphagic Otsuka Long-Evans Tokushima Fatty rats.Journal of applied physiology (Bethesda, Md. : 1985) · 2010Article
- Selenium restores defective beta-adrenergic receptor response of thoracic aorta in diabetic rats.Molecular and cellular biochemistry · 2010Article
- Endothelial dysfunction in the early- and late-stage type-2 diabetic Goto-Kakizaki rat aorta.Molecular and cellular biochemistry · 2009Article
- Early atorvastatin reduces hemorrhage after acute cerebral ischemia in diabetic rats.The Journal of pharmacology and experimental therapeutics · 2009Article
- Glycemic control prevents microvascular remodeling and increased tone in type 2 diabetes: link to endothelin-1.American journal of physiology. Regulatory, integrative and comparative physiology · 2009Article
- Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation.American journal of physiology. Cell physiology · 2009Article
- Differential effects of diet-induced dyslipidemia and hyperglycemia on mesenteric resistance artery structure and function in type 2 diabetes.The Journal of pharmacology and experimental therapeutics · 2009Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Insulin resistance involves decreased phosphorylation of insulin receptor substrate (IRS) proteins and (or) Akt. In the vasculature, modulated Akt phosphorylation may cause impaired vasorelaxation via decreased eNOS activation. Diet-induced insulin resistance enhances endothelin-1(ET-1)-mediated vasoconstriction and prevents vasodilatation to insulin. Presently, we evaluated insulin-mediated vascular relaxation, assessed molecular markers of the insulin signaling pathway, and determined the involvement of ET-1 in response to insulin by using selective ETA- or ETB-receptor blockade in a lean model of type 2 diabetes. Dose-response curves to insulin (0.01-100 ng/mL) were generated with wire myograph using thoracic aorta rings from control Wistar or diabetic Goto-Kakizaki (GK) rats (n=3-11). Maximal relaxation (Rmax) to insulin was significantly impaired and insulin sensitivity was decreased in the GK group. Preincubation with 1 micromol/L BQ-123 or BQ-788 for ETA- and ETB-receptor blockade, respectively, resulted in improved insulin sensitivity. Immunoblotting for native and phosphorylated Akt and IRS-1 revealed a decrease in Akt activation in the GK group. In vivo hyperinsulinemic euglycemic clamp studies showed decreased glucose utilization in GK rats, indicative of insulin resistance. These findings provide evidence that vascular insulin resistance occurs in a nonobese model of diabetes and that both ET receptor subtypes are involved in vascular relaxation to insulin.
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