The pancreatic β cell and type 1 diabetes: innocent bystander or active participant?

Type 1 diabetes mellitus (T1DM) is a chronic disease resulting from destruction of insulin-producing pancreatic beta cells. Genetic and environmental factors contribute to T1DM onset. Use of high-throughput DNA sequencing has allowed geneticists to perform genome-wide association studies (GWAS) to identify novel gene loci associated with T1DM. Interestingly, >50% of these genes encode products that are expressed in beta cells. These studies, coupled with emerging molecular evidence that beta cells are impaired by gain-of-function or loss-of-function of these loci, suggest an active role for the beta cell in eliciting its own demise. Although immune dysregulation plays a vital role in T1DM pathogenesis, understanding the mechanisms contributing to beta cell failure may lead to new strategies to preserve or improve beta cell function in patients with T1DM.