Insulin-Stimulated Bone Blood Flow and Bone Biomechanical Properties Are Compromised in Obese, Type 2 Diabetic OLETF Rats.
Insulin-Stimulated Bone Blood Flow and Bone Biomechanical Properties Are Compromised in Obese, Type 2 Diabetic OLETF Rats.
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作者：
Dirkes RK;Ortinau LC;Rector RS;Olver TD;Hinton PS
2型糖尿病(T2D)增加骨骼脆性和骨折风险；然而，其潜在机制仍未确定。骨血管功能受损，特别是胰岛素刺激的血管扩张和血流量受损是一种潜在的、尚不清楚的机制。本研究的目的是通过比较高血压性OLETF(OLETF)大鼠和正常血糖对照组OLETF大鼠的股骨生物力学特性、骨小梁微结构和胰岛素刺激的骨血管扩张来确定T2D对其的影响。四周龄雄性OLETF大鼠随机分为两组：2型糖尿病(O-T2D)组和正常血糖对照组(O-CON)。O-T2D被允许自由进食啮齿动物的食物，O-CON接受适度的热量限制(相对于O-T2D的摄入量限制30%)，以保持正常的体重(BW)和血糖，直到40周龄。高血压性O-T2D大鼠的体重、体脂和血糖显著高于O-CON。经体重调整后，O-T2D组大鼠股骨中段横截面积(Tt.Ar)、皮质面积(Ct.Ar)、Ct.Ar/Tt.Ar和极转动惯量均大于O-T2D组。O-T2D和O-CON的股骨全骨生物力学性能无明显差异，但与O-CON相比，O-T2D的组织水平强度和刚度有所降低。μ-CT显示，O-T2D组大鼠骨体积百分比、骨小梁数目和连接密度较O-T2D组减少，骨小梁间距较O-CON组大。O-T2D组和O-CON组的胫骨基础血流量与O-T2D组相似，但O-T2D组的胫骨近端和骨干骨髓对胰岛素刺激的血流反应均低于O-CON组。综上所述，在T2D中，胰岛素刺激的骨血流受损与骨小梁微结构和皮质生物力学特性的有害变化有关，提示血管功能障碍可能在糖尿病骨脆性中起作用。©2017作者。JBMR Plus由威利期刊公司代表美国骨与矿物研究学会出版。
Type 2 diabetes (T2D) increases skeletal fragility and fracture risk; however, the underlying mechanisms remain to be identified. Impaired bone vascular function, in particular insulin‐stimulated vasodilation and blood flow is a potential, yet unexplored mechanism. The purpose of this study was to determine the effects of T2D on femoral biomechanical properties, trabecular microarchitecture, and insulin‐stimulated bone vasodilation by comparison of hyperphagic Otsuka Long‐Evans Tokushima Fatty (OLETF) rats with normoglycemic control OLETF rats. Four‐week old, male OLETF rats were randomized to two groups: type 2 diabetes (O‐T2D) or normoglycemic control (O‐CON). O‐T2D were allowed ad libitum access to a rodent chow diet and O‐CON underwent moderate caloric restriction (30% restriction relative to intake of O‐T2D) to maintain normal body weight (BW) and glycemia until 40 weeks of age. Hyperphagic O‐T2D rats had significantly greater BW, body fat, and blood glucose than O‐CON. Total cross‐sectional area (Tt.Ar), cortical area (Ct.Ar), Ct.Ar/Tt.Ar, and polar moment of inertia of the mid‐diaphyseal femur adjusted for BW were greater in O‐T2D rats versus O‐CON. Whole‐bone biomechanical properties of the femur assessed by torsional loading to failure did not differ between O‐T2D and O‐CON, but tissue‐level strength and stiffness adjusted for BW were reduced in O‐T2D relative to O‐CON. Micro–computed tomography (μCT) of the distal epiphysis showed that O‐T2D rats had reduced percent bone volume, trabecular number, and connectivity density, and greater trabecular spacing compared with O‐CON. Basal tibial blood flow assessed by microsphere infusion was similar in O‐T2D and O‐CON, but the blood flow response to insulin stimulation in both the proximal epiphysis and diaphyseal marrow was lesser in O‐T2D compared to O‐CON. In summary, impaired insulin‐stimulated bone blood flow is associated with deleterious changes in bone trabecular microarchitecture and cortical biomechanical properties in T2D, suggesting that vascular dysfunction might play a causal role in diabetic bone fragility. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.