Islet-on-a-chip provides an optical window into cellular metabolism and insulin secretion

Many labs are actively exploring how beta-cell heterogeneity impacts pancreatic islet glucose-stimulated insulin secretion and type 2 diabetes. In particular, beta cells show significant metabolic variability, yet how this variability ultimately dictates islet function is unclear. Since beta-cells are electrically coupled to one another, we hypothesize that a small fraction of over-active beta-cells dictate islet secretion and would bury an underlying phenotype that determines progression of the disease. Our goal is to simultaneously assay: (i) beta-cell metabolic heterogeneity using quantitative fluorescence microscopy (e.g. genetically encoded metabolic sensors) and (ii) pancreatic islet function using microfluidic chip fluorescence assays. Islets in our islet-on-a-chip devices are held against a glass coverslip facilitating live cell imaging with controlled non-turbulent laminar flow. My talk will summarize our efforts to build fluorescence sensors into these devices to dynamically assay oxygen consumption rate (OCR) and insulin secretion.