title: Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Fowlkes
authors.forename: Jeffry S
authors.initials: JS
authors.lastname: Nyman
authors.forename: R Clay
authors.initials: RC
authors.lastname: Bunn
authors.forename: Chanhee
authors.initials: C
authors.lastname: Jo
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wahl
authors.forename: Lichu
authors.initials: L
authors.lastname: Liu
authors.forename: Gael E
authors.initials: GE
authors.lastname: Cockrell
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Morris
authors.forename: Charles K
authors.initials: CK
authors.lastname: Lumpkin
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Thrailkill
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006943:Hyperglycemia / Q000188:drug therapy; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects
chemical_list: D007334:Insulin-Like Growth Factor I
keywords: Bone formation; Diabetes; Distraction osteogenesis; IGF-I