Abstract
Type 2 diabetes, characterized by malfunction of pancreatic β cells, is affected by multiple cues including sex differences. Nevertheless, mechanisms of sex differences in type 2 diabetes susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq) technology, we showed that sexual dimorphism of transcriptome exists in both mouse and human β cells, and differs significantly in human under diabetic condition. Our analysis further revealed the existence of sex-dependent type 2 diabetes altered genes in both mice and human beings, suggesting divergences in pathological mechanisms of type 2 diabetes between sexes. Our results indicated that sex should be taken into consideration when treating diabetes, which was further validated by the sex-matched and sex-mismatched islet transplantation in mice. Compared to sex-matched transplants, sex-mismatched transplants showed downregulation of genes involved in the longevity regulating pathway in β cells and led to impaired glucose tolerance in diabetic mice. Taken together, our findings could advance current understanding of type 2 diabetes pathogenesis with sexually dimorphic perspectives and provide new insights to the development of precision medicine.
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