Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes.

Fowlkes JL, Nyman JS, Bunn RC, Jo C, Wahl EC, Liu L, Cockrell GE, Morris LM, Lumpkin CK, Thrailkill KM
Bone. 2013 57 (1): 36-40

PMID: 23886838 · PMCID: PMC3789626 · DOI:10.1016/j.bone.2013.07.017

OBJECTIVE - Using a streptozotocin (STZ)-induced mouse model of type 1 diabetes (T1D), we have previously demonstrated that long-term diabetes inhibits regenerative bone formation during tibial distraction osteogenesis (DO) and perturbs skeletal integrity by decreasing cortical thickness, bone mineral density and bone's resistance to fracture. Because long-standing T1D is also associated with a deficiency of insulin-like growth factor I (IGF-I), we examined the effects of systemic IGF-I treatment on skeletal microarchitecture and strength, as well as on bone formation in diabetic mice.

RESEARCH DESIGN AND METHODS - Streptozotocin-induced diabetic or control mice were treated with recombinant human IGF-I (rhIGF-I, 1.5mg/kg/day as subcutaneous infusion) or vehicle throughout a 14day DO procedure. Thereafter, trunk blood was assayed for glucose, insulin, rhIGF-I, mouse IGF-I and leptin. Bone formation in distracted tibiae was quantified. Effects on cortical bone strength and trabecular bone architecture were assessed by μCT analysis and three-point bend testing of contralateral femurs.

RESULTS - New bone formation during DO was reduced in diabetic mice but significantly improved with rhIGF-I treatment. The contralateral femurs of diabetic mice demonstrated significant reductions in trabecular thickness, yield strength and peak force of cortical bone, which were improved with rhIGF-I treatment. rhIGF-I also reduced intracortical porosity in control mice. However, treatment with rhIGF-I did not normalize serum glucose, or correct concurrent deficiencies of insulin or leptin seen in diabetes.

CONCLUSIONS - These findings demonstrate that despite persistent hyperglycemia, rhIGF-I promoted new bone formation and improved biomechanical properties of bone in a model of T1D, suggesting that it may be useful as a fracture preventative in this disease.

© 2013.

MeSH Terms (6)

Animals Diabetes Mellitus, Type 1 Hyperglycemia Insulin-Like Growth Factor I Mice Osteogenesis

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