Nuche-Berenguer Bernardo, Moreno Paola, Esbrit Pedro, Dapía Sonia, Caeiro José R, Cancelas Jesús, Haro-Mora Juan J, Villanueva-Peñacarrillo María L
Department of Metabolism, Nutrition, and Hormones, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, Madrid, Spain.
Calcif Tissue Int. 2009 Jun;84(6):453-61. doi: 10.1007/s00223-009-9220-3. Epub 2009 Feb 15.
It has been suggested that hormones released after nutrient absorption, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 2 (GLP-2), could be responsible for changes in bone resorption. However, information about the role of GLP-1 in this regard is scanty. Diabetes-related bone loss occurs as a consequence of poor control of glucose homeostasis, but the relationship between osteoporosis and type 2 diabetes remains unclear. Since GLP-1 is decreased in the latter condition, we evaluated some bone characteristics in streptozotocin-induced type 2 diabetic (T2D) and fructose-induced insulin-resistant (IR) rat models compared to normal (N) and the effect of GLP-1 or saline (control) treatment (3 days by osmotic pump). Blood was taken before and after treatment for plasma measurements; tibiae and femora were collected for gene expression of bone markers (RT-PCR) and structure (microCT) analysis. Compared to N, plasma glucose and insulin were, respectively, higher and lower in T2D; osteocalcin (OC) and tartrate-resistant alkaline phosphatase 5b were lower; phosphate in IR showed a tendency to be higher; PTH was not different in T2D and IR; all parameters were unchanged after GLP-1 infusion. Bone OC, osteoprotegerin (OPG) and RANKL mRNA were lower in T2D and IR; GLP-1 increased OC and OPG in all groups and RANKL in T2D. Compared to N, trabecular bone parameters showed an increased degree of anisotropy in T2D and IR, which was reduced after GLP-1. These findings show an insulin-independent anabolic effect of GLP-1 and suggest that GLP-1 could be a useful therapeutic agent for improving the deficient bone formation and bone structure associated with glucose intolerance.
有人提出，营养物质吸收后释放的激素，如葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽2（GLP - 2），可能是骨吸收变化的原因。然而，关于GLP - 1在这方面作用的信息却很少。糖尿病相关的骨质流失是葡萄糖稳态控制不佳的结果，但骨质疏松症与2型糖尿病之间的关系仍不清楚。由于在后者情况下GLP - 1会减少，我们评估了链脲佐菌素诱导的2型糖尿病（T2D）和果糖诱导的胰岛素抵抗（IR）大鼠模型与正常（N）大鼠相比的一些骨骼特征，以及GLP - 1或生理盐水（对照）治疗（通过渗透泵给药3天）的效果。在治疗前后采集血液进行血浆测量；收集胫骨和股骨用于骨标志物的基因表达（RT - PCR）和结构（显微CT）分析。与N组相比，T2D组的血浆葡萄糖和胰岛素分别更高和更低；骨钙素（OC）和抗酒石酸碱性磷酸酶5b更低；IR组的磷酸盐有升高的趋势；T2D组和IR组的甲状旁腺激素（PTH）没有差异；GLP - 1输注后所有参数均未改变。T2D组和IR组的骨OC、骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）mRNA较低；GLP - 1使所有组的OC和OPG增加，T2D组的RANKL增加。与N组相比，T2D组和IR组的小梁骨参数显示各向异性程度增加，GLP - 1治疗后这种情况有所减轻。这些发现表明GLP - 1具有不依赖胰岛素的合成代谢作用，并提示GLP - 1可能是一种有用的治疗药物，用于改善与葡萄糖不耐受相关的骨形成不足和骨结构问题。
