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      Nebivolol improves insulin sensitivity in the TGR(Ren2)27 rat.

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          Abstract

          Hypertension is often associated with increased oxidative stress and systemic insulin resistance. Use of β-adrenergic receptor blockers in hypertension is limited because of potential negative influence on insulin sensitivity and glucose homeostasis. We sought to determine the impact of nebivolol, a selective vasodilatory β₁-adrenergic blocker, on whole-body insulin sensitivity, skeletal muscle oxidative stress, insulin signaling, and glucose transport in the transgenic TG(mRen2)27 rat (Ren2). This rodent model manifests increased tissue renin angiotensin expression, excess oxidative stress, and whole-body insulin resistance. Young (age, 6-9 weeks) Ren2 and age-matched Sprague-Dawley control rats were treated with nebivolol 10 mg/(kg d) or placebo for 21 days. Basal measurements were obtained for glucose and insulin to calculate the homeostasis model assessment. In addition, insulin metabolic signaling, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reactive oxygen species, and ultrastructural changes as evaluated by transmission electron microscopy were examined ex vivo in skeletal muscle tissue. The Ren2 rat demonstrated systemic insulin resistance as examined by the homeostasis model assessment, along with impaired insulin metabolic signaling in skeletal muscle. This was associated with increased oxidative stress and mitochondrial remodeling. Treatment with nebivolol was associated with improvement in insulin resistance and decreased NADPH oxidase activity/levels of reactive oxygen species in skeletal muscle tissue. Nebivolol treatment for 3 weeks reduces NADPH oxidase activity and improves systemic insulin resistance in concert with reduced oxidative stress in skeletal muscle in a young rodent model of hypertension, insulin resistance, and enhanced tissue RAS expression.

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          Author and article information

          Journal
          Metab. Clin. Exp.
          Metabolism: clinical and experimental
          Elsevier BV
          1532-8600
          0026-0495
          Dec 2011
          : 60
          : 12
          Affiliations
          [1 ] Diabetes Cardiovascular Center of Excellence, University of Missouri-Columbia School of Medicine, Columbia, MO 65212, USA.
          Article
          S0026-0495(11)00112-0 NIHMS292332
          10.1016/j.metabol.2011.04.009
          3170670
          21640361
          a97a6c27-5db3-4729-8ebc-c7ba4471adac
          History

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