Abstract：
Diabetic osteoporosis (DOP) is a diabetic complication associated with a significant disability rate. Liraglutide, a glucagon-like peptide-1 receptor agonist, is a promising and innovative drug for type 2 diabetes mellitus (T2DM), with potential therapeutic implications for bone disorders. This investigation examined the impact of liraglutide on osteoporosis in rats with T2DM and studied the influence of vitamin D receptor Bsm1 polymorphism on liraglutide-induced outcomes. Thirty rats were divided into control, T2DM induced by a combination of a high-fat diet and 25 mg/kg streptozotocin, and T2DM-liraglutide (T2DM treated with 0.4 mg/kg/day liraglutide) groups. After 8 weeks of liraglutide treatment, femurs and blood samples were obtained from all rats for subsequent investigations. Diabetes induced a remarkable rise in the serum levels of receptor activator of nuclear factor kappa B ligand (RANKL) and C-telopeptide of type I collagen (CTX-1) associated with a remarkable decline in osteocalcin and osteoprotegerin (OPG). Impaired bone architecture was also demonstrated by light and scanning electron microscopic study. The immune expression of OPG was down-regulated, while RANKL was up-regulated. Interestingly, the administration of liraglutide ameliorated the previous changes induced by diabetes mellitus. In conclusion, liraglutide can prevent DOP, mostly due to liraglutide\'s ability to increase bone growth, while inhibiting bone resorption.
摘要：
糖尿病性骨质疏松症（DOP）是一种与严重残疾率相关的糖尿病并发症。利拉鲁肽,胰高血糖素样肽-1受体激动剂，是治疗2型糖尿病（T2DM）的有前途的创新药物，对骨骼疾病具有潜在的治疗意义。这项研究研究了利拉鲁肽对T2DM大鼠骨质疏松症的影响，并研究了维生素D受体BsM1多态性对利拉鲁肽诱导的预后的影响。将30只大鼠分为对照组，高脂饮食和25mg/kg链脲佐菌素联合诱导2型糖尿病,和T2DM-利拉鲁肽（T2DM用0.4mg/kg/天的利拉鲁肽治疗）组。利拉鲁肽治疗8周后，从所有大鼠获得股骨和血液样本用于后续研究。糖尿病引起血清核因子κB受体激活剂配体（RANKL）和I型胶原C端肽（CTX-1）水平的显着升高，与骨钙蛋白和骨保护素（OPG）的显着下降有关。光和扫描电子显微镜研究也证明了受损的骨结构。OPG的免疫表达下调,而RANKL上调。有趣的是,利拉鲁肽的给药改善了以前由糖尿病引起的变化。总之,利拉鲁肽可以预防DOP，主要是由于利拉鲁肽增加骨骼生长的能力，同时抑制骨吸收。
