Engineering-inspired approaches to study β-cell function and diabetes.

Strategies to mitigate the pathologies from diabetes range from simply administering insulin to prescribing complex drug/biologic regimens combined with lifestyle changes. There is a substantial effort to better understand β-cell physiology during diabetes pathogenesis as a means to develop improved therapies. The convergence of multiple fields ranging from developmental biology to microfluidic engineering has led to the development of new experimental systems to better study complex aspects of diabetes and β-cell biology. Here we discuss the available insulin-secreting cell types used in research, ranging from primary human β-cells, to cell lines, to pluripotent stem cell-derived β-like cells. Each of these sources possess inherent strengths and weaknesses pertinent to specific applications, especially in the context of engineered platforms. We then outline how insulin-expressing cells have been used in engineered platforms and how recent advances allow for better mimicry of in vivo conditions. Chief among these conditions are β-cell interactions with other endocrine organs. This facet is beginning to be thoroughly addressed by the organ-on-a-chip community, but holds enormous potential in the development of novel diabetes therapeutics. Furthermore, high throughput strategies focused on studying β-cell biology, improving β-cell differentiation, or proliferation have led to enormous contributions in the field and will no doubt be instrumental in bringing new diabetes therapeutics to the clinic. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: While superficially a disease of insulin secretion and sugar metabolism, the deeper complexities of diabetes necessitate advanced engineered strategies to uncover new treatment approaches. In vitro models of β-cells and insulin secretion in a human-specific context have therefore emerged as powerful tools to study diabetes. In this concise review, we discuss several advances including different sources of insulin-secreting cells, organ-on-a-chip models, and high throughput strategies designed to deepen our understanding of β-cell biology and to better treat disease.