Sexual dimorphisms in pancreatic β-cell transcriptome and their implications for therapy

Diabetes currently affects 8% of the global population and continues to rise. The two main types of diabetes are Type 1 diabetes (T1D) caused by the auto-immune destruction of beta cells and Type 2 diabetes (T2D) characterized by the inability to respond to insulin in combination with beta cell dysfunction. The prevalence of both types of diabetes is higher in males than females. This can be explained by gender-associated differences in beta cell function and susceptibility to beta cell failure. The genetics behind these differences is poorly understood. In this project I will use RNA sequencing to determine and compare the transcriptomes of male and female mouse beta cells to identify sex biased gene expression. Genes of interest will be characterized in vitro using the human beta cell line, EndoC-BH3, and in vivo using transgenic mice. For the latter, we will use a pAV-CreOn-shRNA expression cassette delivered by an Adenovirus associated virus in InsCre mice, to knock down selected genes in the beta cell and study the physiological consequences. It is anticipated that the identification of genes with sex-biased expression and physiological and pathological responses in the beta cell will be leveraged towards gender-specific therapies.