Abstract
Islet perifusion systems can be used to monitor the highly dynamic insulin release of pancreatic islets in glucose-stimulated insulin secretion (GSIS) assays. Here, we present a new generation of the microfluidic hanging-drop-based islet perifusion platform that was developed to study the alterations in insulin secretion dynamics from single pancreatic islet microtissues at high temporal resolution. The platform was completely redesigned to increase experimental throughput and to reduce operational complexity. The experimental throughput was increased fourfold by implementing a network of interconnected hanging drops, which allows for performing GSIS assays with four individual islet microtissues in parallel with a sampling interval of 30 s. We introduced a self-regulating drop-height mechanism that enables continuous flow and maintains a constant liquid volume in the chip, which enables simple and robust operation. Upon glucose stimulation, reproducible biphasic insulin release was simultaneously observed from all islets in the system. The measured insulin concentrations showed low sample-to-sample variation as a consequence of precise liquid handling with stable drop volumes, equal flow rates in the channels, and accurately controlled sampling volumes in all four drops. The presented device will be a valuable tool in islet and diabetes research for studying dynamic insulin secretion from individual pancreatic islets.
Highlights
Langerhans islets are micro-organs in the pancreas, which secrete hormones that help maintain glucose homeostasis in the human body
Islet perifusion systems need to provide a constant flow of media around the islets
Continuous flow and sampling of the perfused media allows for capturing islet-secreted hormones at defined time points. The intervals between these time points should be short enough to resolve the dynamics of hormone release
Summary
Langerhans islets are micro-organs in the pancreas, which secrete hormones that help maintain glucose homeostasis in the human body. The islets are composed of different endocrine cell types, of which pancreatic beta-cells are the most common ones. They release insulin in a highly dynamic, bi-phasic and pulsatile manner in response to elevated glucose levels in the blood (In’t Veld and Marichal, 2010). Studying this highly dynamic process of glucose-stimulated insulin secretion (GSIS) of pancreatic islets can give insights into the insulin release mechanisms of healthy and diabetic islets. Reliable technological methods and platforms to characterize islets as well as relevant and reproducible islet model systems are scarce
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