Mouse Single Islet β Cell Transcriptomic Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes.

Type 2 diabetes (T2D), characterized by the malfunction of pancreatic β cells, is affected by multiple factors, including sex differences. However, the mechanisms of sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we show sexually dimorphic transcriptomes exist in mouse β cells. Using a high-fat diet induced T2D mouse model, our work reveals the existence of sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Our results, including sex-matched and sex-mismatched islet transplantation experiments in mice, suggest sex should be considered when treating T2D. As compared to sex-matched transplants, sex-mismatched transplants showed downregulation of genes involved in the longevity regulating pathway of β cells and led to impaired glucose tolerance in diabetic mice. Taken together, our findings further implicate sexual dimorphism in T2D pathogenicity and provides novel insights towards the development of precision medicine in T2D.