Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab Emirates.
Cranfield Forensic Institute, Cranfield University, Shrivenham, United Kingdom.
PeerJ. 2023 Oct 17;11:e16278. doi: 10.7717/peerj.16278. eCollection 2023.
Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone.
DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques.
It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21-28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples < 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels < 0.001, increased the serum CTX1 levels < 0.05, and also showed non-significant improvement in osteocalcin levels.
This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.
骨质疏松症是 1 型糖尿病（DM1）的一种重要合并症，会增加骨折风险。低剂量的运动诱导激素“鸢尾素”已被证明通过增加成骨细胞分化和减少破骨细胞成熟、抑制细胞凋亡和炎症，对骨代谢有有益的影响。我们通过观察其对小梁骨的作用来研究鸢尾素在治疗糖尿病性骨病中的作用。
通过腹腔注射链脲佐菌素 60mg/kg 体重诱导 DM1。将低剂量的鸢尾素（每周两次，每次 5μg，腹腔内注射，共 6 周）注射到一半的对照和 4 周龄糖尿病雄性 Wistar 大鼠中。糖尿病诱导 6 个月后处死动物。使用 micro-CT 技术分析股骨头和颈部的小梁骨。使用 ELISA、Western blot 和 RT-PCR 技术测量骨转换标志物。
结果发现，DM1 通过增加小梁分离度（Tb-Sp）和降低小梁厚度（Tb-Th）、骨体积分数（BV/TV）和骨密度（BMD）来恶化小梁骨微结构。鸢尾素治疗通过增加小梁数量（<0.05）对骨质量产生积极影响，并使 BMD、Tb-Sp 和 BV/TV 增加 21-28%。骨微结构的恶化主要归因于骨形成减少，在糖尿病骨样本中观察到低骨钙素和高硬骨素水平（<0.001）。鸢尾素治疗显著抑制血清和骨硬骨素水平（<0.001），增加血清 CTX1 水平（<0.05），并使骨钙素水平略有改善。
这是我们所知的第一项初步研究，表明低剂量的鸢尾素可轻微改善 DM1 中的小梁骨，并且是一种有效的降低硬骨素水平的肽。
