Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Rats

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dc.contributor.authorBortolin, Raul Hernandes
dc.contributor.authorFreire Neto, Francisco Paulo
dc.contributor.authorArcaro, Carlos Alberto [UNESP]
dc.contributor.authorBezerra, Joao Felipe
dc.contributor.authorSilva, Flavio Santos da
dc.contributor.authorGalvao Ururahy, Marcela Abbott
dc.contributor.authorCosta Souza, Karla Simone da
dc.contributor.authorDuarte Moreira Lima, Valeria Morgiana Gualberto
dc.contributor.authorLuchessi, Andre Ducati
dc.contributor.authorLima, Francisco Pignataro
dc.contributor.authorLia Fook, Marcus Vinicius
dc.contributor.authorSilva, Bartolomeu Jorge da
dc.contributor.authorAlmeida, Maria das Gracas
dc.contributor.authorAbreu, Bento Joao
dc.contributor.authorRezende, Luciana Augusto de
dc.contributor.authorRezende, Adriana Augusto de
dc.contributor.institutionUniv Fed Rio Grande do Norte
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionState Univ Paraiba
dc.contributor.institutionUniv Fed Campina Grande
dc.contributor.institutionUniv Ribeirao Preto
dc.date.accessioned2018-11-26T15:43:36Z
dc.date.available2018-11-26T15:43:36Z
dc.date.issued2017-03-01
dc.description.abstractType 1 diabetes mellitus (T1DM) is associated with several skeletal alterations, particularly in conditions of poor glycaemic control. Insulin therapy is the major conservative treatment for T1DM; however, the effects of this hormone on bone markers of T1DM rats are limited, and the regulatory mechanisms remain elusive. Therefore, the evaluation of molecular and non-molecular parameters in a chronic animal model of T1DM-induced bone loss, treated with and without insulin, may help in elucidating the insulin mechanisms. Male Wistar rats were assigned into three groups: control, T1DM (T1DM rats induced with streptozotocin [STZ] at 40 mg/kg intravenously) and T1DM plus insulin therapy (T1DMI). After 8 weeks, we evaluated the serum biochemical, tibia histomorphometric and biomechanical parameters, as well as the gene expression of the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteocalcin (OC) of femur mRNA. Compared with T1DM, the T1DMI group showed less bone loss, which was revealed by the increased trabecular width (TbWi, p < 0.001) and trabecular bone area (BAr, p < 0.01), reduced trabecular separation (TbSp, p < 0.01) and increased Young's modulus (p < 0.05). Moreover, molecular analyses indicated that the expression of OPG and OC was up-regulated (p < 0.001 and p < 0.05, respectively). In summary, the up-regulation of OPG and OC in the T1DMI group supports an anabolic effect of insulin, which was demonstrated by the maintenance of bone architecture and flexibility. These results suggest that insulin therapy may prevent T1DM-induced bone loss via the effects on the bone formation.en
dc.description.affiliationUniv Fed Rio Grande do Norte, Dept Clin & Toxicol Anal, Natal, RN, Brazil
dc.description.affiliationUniv Fed Rio Grande do Norte, Dept Biochem, Natal, RN, Brazil
dc.description.affiliationSao Paulo State Univ, Dept Clin Anal, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Rio Grande do Norte, Dept Morphol, Natal, RN, Brazil
dc.description.affiliationState Univ Paraiba, Dept Pharm, Campina Grande, Paraiba, Brazil
dc.description.affiliationUniv Fed Rio Grande do Norte, Dept Clin Pathol, Natal, RN, Brazil
dc.description.affiliationUniv Fed Campina Grande, Lab Evaluat & Dev Biomat, Campina Grande, Paraiba, Brazil
dc.description.affiliationUniv Ribeirao Preto, Dept Chem, Sao Paulo, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Dept Clin Anal, Sao Paulo, Brazil
dc.description.sponsorshipUNAERP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent227-234
dc.identifierhttp://dx.doi.org/10.1111/bcpt.12672
dc.identifier.citationBasic & Clinical Pharmacology & Toxicology. Hoboken: Wiley-blackwell, v. 120, n. 3, p. 227-234, 2017.
dc.identifier.doi10.1111/bcpt.12672
dc.identifier.issn1742-7835
dc.identifier.urihttp://hdl.handle.net/11449/159398
dc.identifier.wosWOS:000394538600003
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBasic & Clinical Pharmacology & Toxicology
dc.relation.ispartofsjr0,655
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.titleAnabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Ratsen
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dcterms.rightsHolderWiley-Blackwell

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