title: Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Rats.
abstract: Type 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.
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Raul Hernandes
authors.initials: RH
authors.lastname: Bortolin
authors.affiliation: Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Francisco Paulo
authors.initials: FP
authors.lastname: Freire Neto
authors.affiliation: Department of Clinical Analyses, São Paulo State University, Araraquara, São Paulo, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Arcaro
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: João Felipe
authors.initials: JF
authors.lastname: Bezerra
authors.affiliation: Department of Morphology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Flávio Santos
authors.initials: FS
authors.lastname: da Silva
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Marcela Abbott Galvão
authors.initials: MA
authors.lastname: Ururahy
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Karla Simone da Costa
authors.initials: KS
authors.lastname: Souza
authors.affiliation: Department of Pharmacy, State University of Paraíba, Campina Grande, Paraíba, Brazil.
authors.forename: Valeria Morgiana Gualberto Duarte Moreira
authors.initials: VM
authors.lastname: Lima
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: André Ducati
authors.initials: AD
authors.lastname: Luchessi
authors.affiliation: Department of Clinical Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Francisco Pignataro
authors.initials: FP
authors.lastname: Lima
authors.affiliation: Laboratory of Evaluation and Development of Biomaterials, Federal University of Campina Grande, Campina Grande, Paraíba, Brazil.
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Lia Fook
authors.affiliation: Laboratory of Evaluation and Development of Biomaterials, Federal University of Campina Grande, Campina Grande, Paraíba, Brazil.
authors.forename: Bartolomeu Jorge
authors.initials: BJ
authors.lastname: da Silva
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Maria das Graças
authors.initials: MD
authors.lastname: Almeida
authors.affiliation: Department of Morphology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Bento João
authors.initials: BJ
authors.lastname: Abreu
authors.affiliation: Department of Chemistry, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Luciana Augusto
authors.initials: LA
authors.lastname: de Rezende
authors.affiliation: Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Adriana Augusto
authors.initials: AA
authors.lastname: de Rezende
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005269:Femur / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D015675:Osteocalcin / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000473:pathology; D015854:Up-Regulation
chemical_list: D045930:Anabolic Agents; D007328:Insulin; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C506032:Tnfrsf11b protein, rat; D015675:Osteocalcin