Inhibition Of 72 Kda Inositol Polyphosphate 5-phosphatase E Improves Insulin Signal Transduction In Diet-induced Obesity.

dc.creatorBertelli, Daniela F
dc.creatorCoope, Andressa
dc.creatorCaricilli, Andrea M
dc.creatorPrada, Patricia O
dc.creatorSaad, Mario J
dc.creatorVelloso, Licio A
dc.creatorAraujo, Eliana P
dc.date2013-May
dc.date2015-11-27T13:31:16Z
dc.date2015-11-27T13:31:16Z
dc.date.accessioned2018-03-29T01:17:05Z
dc.date.available2018-03-29T01:17:05Z
dc.identifierThe Journal Of Endocrinology. v. 217, n. 2, p. 131-40, 2013-May.
dc.identifier1479-6805
dc.identifier10.1530/JOE-12-0562
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/23349329
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/200454
dc.identifier23349329
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1300687
dc.descriptionThe 72 kDa inositol polyphosphate 5-phosphatase E (72k-5ptase) controls signal transduction through the catalytic dephosphorylation of the 5-position of membrane-bound phosphoinositides. The reduction of 72k-5ptase expression in the hypothalamus results in improved hypothalamic insulin signal transduction and reduction of food intake and body mass. Here, we evaluated the tissue distribution and the impact of obesity on the expression of 72k-5ptase in peripheral tissues of experimental animals. In addition, insulin signal transduction and action were determined in an animal model of obesity and insulin resistance treated with an antisense (AS) oligonucleotide that reduces 72k-5ptase expression. In lean Wistar rats, 72k-5ptase mRNA and protein are found in highest levels in heart, skeletal muscle, and white adipose tissue. In three distinct models of obesity, Wistar rats, Swiss mice fed on high-fat diet, and leptin-deficient ob/ob mice, the expression of 72k-5ptase is increased in skeletal muscle and adipose tissue. The treatment of obese Wistar rats with an anti-72k-5ptase AS oligonucleotide results in significant reduction of 72k-5ptase catalytic activity, which is accompanied by reduced food intake and body mass and improved insulin signal transduction and action as determined by immunoblotting and clamp studies respectively. 72k-5ptase expression is increased in obesity and its AS inhibition resulted in a significant improvement in insulin signal transduction and restoration of glucose homeostasis.
dc.description217
dc.description131-40
dc.languageeng
dc.relationThe Journal Of Endocrinology
dc.relationJ. Endocrinol.
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAdipose Tissue, White
dc.subjectAnimals
dc.subjectDiet, High-fat
dc.subjectDisease Models, Animal
dc.subjectInsulin
dc.subjectInsulin Resistance
dc.subjectLeptin
dc.subjectMale
dc.subjectMice
dc.subjectMice, Obese
dc.subjectMuscle, Skeletal
dc.subjectMyocardium
dc.subjectObesity
dc.subjectOligoribonucleotides, Antisense
dc.subjectPhosphoric Monoester Hydrolases
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectSignal Transduction
dc.titleInhibition Of 72 Kda Inositol Polyphosphate 5-phosphatase E Improves Insulin Signal Transduction In Diet-induced Obesity.
dc.typeArtículos de revistas


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