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Type: Artigo
Title: Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice
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Author: Leiria, Luiz O.
Sollon, Carolina
Calixto, Marina C.
Lintomen, Leticia
Monica, Fabiola Z.
Anhe, Gabriel F.
De Nucci, Gilberto
Zanesco, Angelina
Grant, Andrew D.
Antunes, Edson
Abstract: Obesity/metabolic syndrome are common risk factors for overactive bladder. This study aimed to investigate the functional and molecular changes of detrusor smooth muscle (DSM) in high-fat insulin resistant obese mice, focusing on the role of protein kinase C (PKC) and Ca(v)1.2 in causing bladder dysfunction. Male C57BL/6 mice were fed with high-fat diet for 10 weeks. In vitro functional responses and cystometry, as well as PKC and Ca(v)1.2 expression in bladder were evaluated. Obese mice exhibited higher body weight, epididymal fat mass, fasting glucose and insulin resistance. Carbachol (0.001-100 mu M), alpha,beta-methylene ATP (1-10 mu M), KCl (1-300 mM), extracellular Ca2+ (0.01-100 mM) and phorbol-12,13-dibutyrate (PDBu; 0.001-3 mu M) all produced greater DSM contractions in obese mice, which were fully reversed by the Ca(v)1.2 blocker amlodipine. Cystometry evidenced augmented frequency, non-void contractions and post-void pressure in obese mice that were also prevented by amlodipine. Metformin treatment improved the insulin sensitivity, and normalized the in vitro bladder hypercontractility and cystometric dysfunction in obese mice. The PKC inhibitor GF109203X (1 mu M) also reduced the carbachol induced contractions. PKC protein expression was markedly higher in bladder tissues from obese mice, which was normalized by metformin treatment. The Ca(v)1.2 channel protein expression was not modified in any experimental group. Our findings show that Ca(v)1.2 blockade and improvement of insulin sensitization restores the enhanced PKC protein expression in bladder tissues and normalizes the overactive detrusor. It is likely that insulin resistance importantly contributes for the pathophysiology of this urological disorder in obese mice
Subject: Adiposidade
Peso corporal
Cloreto de cálcio
Country: Estados Unidos
Editor: Public Library of Science
Citation: Plos ONE. Public Library Science, v.7, n.11, 2012
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0048507
Date Issue: 2012
Appears in Collections:FCM - Artigos e Outros Documentos

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