Type 2 diabetes mellitus (T2DM) commonly affects the bone mineral phase and advanced glycation end-products (AGEs) which eventually led to changes in bone material properties on the nano and macro-scale. Several anti-diabetic compounds are widely used to control high blood sugar or glucose caused by T2DM. Low Dose Naltrexone (LDN), an opiate receptor antagonist, and a known TLR4 antagonist, treatment can improve glucose tolerance and insulin sensitivity in high-fat-diet (HFD) induced T2DM mice. However, the influences of LDN on the local bone quality, mineralization of the bone, and the skeletal AGEs levels have not been fully elucidated. The objective of this study is to understand the effect of LDN on Raman assisted bone quality, skeletal AGEs (determined by Raman spectroscopy), and nano-mechanical properties in HFD induced T2DM mice bone. In order to investigate these, mice and corresponding bones were divided into four groups (divided based on diet and treatment), (a) normal control diet treated with saline water, (b) normal control diet treated with LDN, (c) HFD treated with saline water, and (d) HFD treated with LDN. In T2DM condition (HFD treated with saline water), alteration of Raman-based compositional measures in bone quality including mineral-to-matrix ratios, carbonate substitution, mineral crystallinity, and collagen quality was observed. Our data also indicated that T2DM enhances the skeletal AGEs, and impairs the nano-mechanical properties. Interestingly, present results indicated that LDN controls the Raman-based compositional measures in bone quality in HFD induced T2DM mice bone. Additionally, LDN also protects the alteration of the skeletal AGEs levels and nano-mechanical properties in T2DM mice bone. This study concluded that LDN can control the HFD induced T2DM affected bone abnormalities at multiple hierarchical levels.

2型糖尿病（T2DM）通常会影响骨矿物质相和晚期糖基化终产物（AGEs），最终导致纳米和宏观尺度上的骨材料特性发生变化。几种抗糖尿病化合物被广泛用于控制由T2DM引起的高血糖或血糖。低剂量纳曲酮（鸦片受体拮抗剂）和已知的TLR4拮抗剂可改善高脂饮食（HFD）诱导的T2DM小鼠的葡萄糖耐量和胰岛素敏感性。但是，LDN对局部骨质量，骨矿化和骨骼AGEs水平的影响尚未完全阐明。这项研究的目的是了解LDN对HFD诱导的T2DM小鼠骨骼的拉曼辅助骨骼质量，骨骼AGEs（由拉曼光谱测定）和纳米力学性能的影响。为了对此进行研究，将小鼠和相应的骨骼分为四组（根据饮食和治疗方法划分），（a）用盐水处理的正常对照饮食，（b）用LDN处理的正常对照饮食，（c）用HFD处理（d）将HFD用LDN处理。在T2DM条件下（用盐水进行HFD处理），观察到了基于拉曼的骨质测量指标的变化，包括矿物质与基质的比率，碳酸盐替代，矿物质结晶度和胶原蛋白质量。我们的数据还表明，T2DM增强了骨骼的年龄，并损害了纳米机械性能。有趣的是，目前的结果表明，LDN控制着HFD诱导的T2DM小鼠骨骼中骨质量的基于拉曼的成分测量。此外，LDN还可以保护T2DM小鼠骨骼中骨骼AGEs水平的改变和纳米机械性能。这项研究得出的结论是，LDN可以在多个层次上控制HFD诱导的T2DM感染的骨骼异常。