Continuous subcutaneous insulin infusion ameliorates bone structures and mechanical properties in type 2 diabetic rats by regulating bone remodeling.

Abstract

Continuous subcutaneous insulin infusion (CSII) is an intensive insulin therapy for patients with type 2 diabetes mellitus (T2DM) who have poor glycemic control, but its effect on T2DM-related bone disorder is unclear. This study described the possible mechanisms by which CSII affects bone remodeling, structures, and mechanical properties in T2DM rats. Herein, male rats (6-week-old) were assigned randomly to 4-week and 8-week administration groups, each of which included healthy control, T2DM, CSII, and Placebo groups. Then, metabolic markers, bone formation and resorption markers in serum and protein expressions of osteoclastogenesis regulators in tibias were detected. Meanwhile, microstructures, nanostructures, macro-mechanical properties, nano-mechanical properties, and mineral compositions in femurs were evaluated. 4-week later, CSII treatment restored circulatory metabolites, bone formation and resorption markers, and osteoclastogenesis regulators, improved certain bone microstructures, decreased matrix mineralization, and increased fracture toughness in T2DM rats. For 8-week group, CSII treatment restored bone formation and resorption markers, osteoclastogenesis regulators, and bone microstructures, besides improved bone mineral compositions and nanostructures, enhanced bone mechanical properties such as fracture toughness, maximum load, elastic modulus, indentation modulus and hardness. Collectively, 8-week CSII treatment is more conducive to ameliorating bone structures and mechanical properties in T2DM rats by regulating bone remodeling compared with 4-week CSII treatment, thus improving whole bone quality and providing valuable information for clinical prevention and treatment of T2DM-related bone disorders.