Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes.
Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes.
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胰岛素样生长因子I（IGF-I）在1型糖尿病的小鼠模型中的骨促进作用。
DOI：
10.1016/j.bone.2013.07.017
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发表时间：
2013-11
期刊：
影响因子：
4.1
通讯作者：
Thrailkill, Kathryn M.
中科院分区：
文献类型：
--
作者：
Fowlkes, John L.;Nyman, Jeffry S.;Bunn, R. Clay;Jot, Chanhee;Wahl, Elizabeth C.;Liu, Lichu;Cockrell, Gael E.;Morris, Lindsey M.;Lumpkin, Charles K., Jr.;Thrailkill, Kathryn M.
使用链脲佐菌素（STZ）诱导的1型糖尿病（T1 D）小鼠模型，我们以前已经证明，长期糖尿病抑制胫骨牵张成骨（DO）过程中再生骨的形成，并通过降低皮质厚度，骨矿物质密度和骨的抗骨折性来扰乱骨骼的完整性。由于长期存在的T1 D也与胰岛素样生长因子I（IGF-I）缺乏有关，我们研究了全身IGF-I治疗对骨骼微结构和强度以及糖尿病小鼠骨形成的影响。在整个14天DO程序中，用重组人IGF-I（rhIGF-I，1.5mg/kg/天，皮下输注）或载体处理链脲霉素诱导的糖尿病小鼠或对照小鼠。此后，测定躯干血的葡萄糖、胰岛素、rhIGF-I、小鼠IGF-I和瘦素。对牵张胫骨的骨形成进行定量。通过对侧股骨的µCT分析和三点弯曲测试评估对皮质骨强度和松质骨结构的影响。糖尿病小鼠DO期间新骨形成减少，但rhIGF-I治疗显著改善。糖尿病小鼠对侧股骨表现出骨小梁厚度、屈服强度和皮质骨峰值力的显著降低，这些在rhIGF-I治疗后得到改善。rhIGF-I还降低了对照小鼠的皮质内孔隙率。然而，用rhIGF-I治疗不能使血糖正常化，也不能纠正糖尿病中同时出现的胰岛素或瘦素缺乏。这些发现表明，尽管持续高血糖，rhIGF-I促进新骨形成和改善T1 D模型中骨的生物力学性质，这表明它可能是有用的，作为预防这种疾病的骨折。
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. Streptozotocin-induced diabetic or control mice were treated with recombinant human IGF-I (rhIGF-I, 1.5 mg/kg/day as subcutaneous infusion) or vehicle throughout a 14 day 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. 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. 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.
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DOI：
10.1359/jbmr.080713
发表时间：
2008-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Moyer-Mileur LJ;Slater H;Jordan KC;Murray MA
通讯作者：
Murray MA
影响因子：
4
作者：
Thrailkill, K. M.;Jo, C. -H.;Cockrell, G. E.;Moreau, C. S.;Lumpkin, C. K., Jr.;Fowlkes, J. L.
通讯作者：
Fowlkes, J. L.
影响因子：
6.2
作者：
Fowlkes, John L.;Thrailkill, Kathryn M.;Lumpkin, Charles K., Jr.
通讯作者：
Lumpkin, Charles K., Jr.
影响因子：
8.2
作者：
Agudo, J.;Ayuso, E.;Bosch, F.
通讯作者：
Bosch, F.
影响因子：
2
作者：
Follak, N;Klöting, I;Merk, H
通讯作者：
Merk, H