Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex d...Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear.Using single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβcells.Using a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of T2D.Furthermore,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells.Moreover,the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance.These data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating T2D.We hope that our findings could provide new insights for the development of precision medicine in T2D.展开更多
基金This work was supported by the National Key R&D Program of China(Grant Nos.2016YFA0102200,2017YFA0106500,2018YFA0107102,and 2020YFA0112500 awarded to WL,Grant No.2018YFA0107602 awarded to ZS)Key Project of the Science and Technology Commission of Shanghai Municipality,China(Grant No.19JC1415300 awarded to WL)+2 种基金the National Key R&D Program of China(Grant No.2018YFD0900604 awarded to WS)the National Natural Science Foundation of China(Grant Nos.41676119 and 41476120 awarded to WS)the start-up fund from Ocean University of China(awarded to WS).
文摘Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear.Using single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβcells.Using a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of T2D.Furthermore,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells.Moreover,the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance.These data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating T2D.We hope that our findings could provide new insights for the development of precision medicine in T2D.
