role of pkc and cav1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in micepkc和cav1.2逼尿肌过度活跃的老鼠肥胖与胰岛素抵抗相关的模型.pdfVIP

Role of PKC and CaV1.2 in Detrusor Overactivity in a Model of Obesity Associated with Insulin Resistance in Mice 1 1 1 ´ 1 ´ ´ 1 Luiz O. Leiria , Carolina Sollon , Marina C. Calixto , Letıcia Lintomen , Fabıola Z. Monica , ˆ 1 1 2 3 1 Gabriel F. Anhe , Gilberto De Nucci , Angelina Zanesco , Andrew D. Grant , Edson Antunes * ˜ 1 Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil, 2 Department of Physical Education, Institute ˜ ˜ of Bioscience, University of Sao Paulo State (UNESP), Rio Claro, Sao Paulo, Brazil, 3 Wolfson Centre for Age-Related Diseases, King’s College, London, United Kingdom 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 Cav 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 1.2 expression in bladder were evaluated. Obese v mice exhibited higher body weight, epididymal fat mass, fasting glucose and insulin resistance. Carbachol (0.001–100 mM), a,b-methylene ATP (1–10 mM), KCl (1–300 mM), extracellular Ca2+ (0.01–100 mM)