Diabetes, Metabolic Syndrome and Obesity (Jul 2021)
Osteoclasts May Affect Glucose Uptake-Related Insulin Resistance by Secreting Resistin
Abstract
Xiangqi Li,* Fei Sun,* Jiancan Lu, Jichen Zhang, Jingnan Wang, Hongling Zhu, Mingjun Gu, Junhua Ma Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junhua MaDepartment of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, Miaopu Road 219, Shanghai, 200135, People’s Republic of ChinaTel +86 21 58858730Email [email protected]: Bone may play a role in the modulation of insulin sensitivity. Insulin resistance can be caused by increased resistin. However, whether osteoclasts affect the insulin resistance via resistin remains unclear. In the present study, we show the expression of resistin in osteoclasts and the possible underlying role of resistin on glucose uptake-related insulin resistance in vitro.Methods: Conditioned mediums (CM) were collected from Raw264.7 cells treated without (CCM) or with RANKL (CM3, treated with RANKL for 3 days; CM5, treated with RANKL for 5 days) and transfected with control or resistin siRNA (CMsiRNA). The osteoclast formation was examined by tartrate resistant acid phosphatase (TRAP) staining. C2C12 myoblasts were cultured with the CM or CMsiRNA. Glucose uptake was evaluated by 2-NBDG fluorescence intensity. Resistin expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay. Statistical analysis was performed by an independent two sample t-test or one-way ANOVA.Results: The 2-NBDG fluorescence intensity was higher in C2C12 cells treated with CCM compared to those that received CM3 and CM5 (p < 0.05). Resistin mRNA and protein expressions were both increased in RAW264.7 cells treated with RANKL for 3 days and 5 days compared with those cells without RANKL administration. The 2-NBDG fluorescence intensities in C2C12 cells treated with CMsiRNA and CM5+Anti-resistin antibody were significantly higher than those cultured with CM5 (p < 0.05).Conclusion: Osteoclasts may promote glucose uptake-related insulin resistance by secreting resistin.Keywords: bone, insulin resistance, osteoclast, resisin, diabetes mellitus
