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

• Published in: Basic & clinical pharmacology & toxicology 2017-03, Vol.120 (3), p.227-234
• Main Authors: Bortolin, Raul Hernandes, Freire Neto, Francisco Paulo, Arcaro, Carlos Alberto, Bezerra, João Felipe, Silva, Flávio Santos, Ururahy, Marcela Abbott Galvão, Souza, Karla Simone da Costa, Lima, Valeria Morgiana Gualberto Duarte Moreira, Luchessi, André Ducati, Lima, Francisco Pignataro, Lia Fook, Marcus Vinicius, Silva, Bartolomeu Jorge, Almeida, Maria das Graças, Abreu, Bento João, Rezende, Luciana Augusto, Rezende, Adriana Augusto
• Format: Article
• Language: English
• Subjects: Anabolic Agents - pharmacology; Anabolic Agents - therapeutic use; Animal models; Animals; Biomechanics; Biomedical materials; Bone Density - drug effects; Bone growth; Bone loss; Cancellous bone; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - drug therapy; Femur; Femur - metabolism; Gene expression; Insulin; Insulin - pharmacology; Insulin - therapeutic use; Male; Mechanical properties; Modulus of elasticity; Osteocalcin; Osteocalcin - metabolism; Osteogenesis; Osteoprotegerin; Osteoprotegerin - metabolism; Parameters; RANK Ligand - metabolism; Rats; Rats, Wistar; Regulatory mechanisms (biology); RNA, Messenger - metabolism; Rodents; Streptozocin; Therapy; Tibia; Tibia - pathology; TRANCE protein; Up-Regulation
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.12672

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