Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up‐Regulation in Streptozotocin‐Induced Diabetic Rats |
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| Authors: | Raul Hernandes Bortolin Francisco Paulo Freire Neto Carlos Alberto Arcaro João Felipe Bezerra Flávio Santos da Silva Marcela Abbott Galvão Ururahy Karla Simone da Costa Souza Valeria Morgiana Gualberto Duarte Moreira Lima André Ducati Luchessi Francisco Pignataro Lima Marcus Vinicius Lia Fook Bartolomeu Jorge da Silva Maria das Graças Almeida Bento João Abreu Luciana Augusto de Rezende Adriana Augusto de Rezende |
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| Affiliation: | 1. Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil;2. Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil;3. Department of Clinical Analyses, S?o Paulo State University, Araraquara, S?o Paulo, Brazil;4. Department of Morphology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil;5. Department of Pharmacy, State University of Paraíba, Campina Grande, Paraíba, Brazil;6. Department of Clinical Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil;7. Laboratory of Evaluation and Development of Biomaterials, Federal University of Campina Grande, Campina Grande, Paraíba, Brazil;8. Department of Chemistry, University of Ribeir?o Preto, Ribeir?o Preto, S?o Paulo, Brazil |
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| 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. |
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