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In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High
Patrick M Misun1, Burçak Yesildag2, Felix Forschler1
1Bio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058, Basel, Switzerland.
Insights
A new microfluidic platform enables high-resolution study of glucose-stimulated insulin secretion (GSIS) from single human islets. This method reveals more dynamic insulin release patterns compared to traditional pooled islet assays.
Area of Science:
- Endocrinology
- Biomedical Engineering
- Cell Biology
Background:
- Insulin release from pancreatic islets is biphasic and pulsatile.
- Studying dynamic insulin secretion requires high temporal resolution.
- Existing in vitro methods have limitations in capturing these dynamics.
Purpose of the Study:
- To develop a novel platform for glucose-stimulated insulin secretion (GSIS) assays using single human islets.
- To enable high-resolution study of dynamic insulin release patterns.
- To compare single-islet perifusion with pooled islet assays.
Main Methods:
- Engineered a microfluidic hanging-drop-based perifusion system.
- Developed a standardized human islet microtissue model.
- Performed perifusion assays with rapid glucose switching and short sampling intervals.
Main Results:
- Human islet microtissues showed robust, long-term glucose responsiveness and reproducible dynamic GSIS.
- Single-islet perifusion yielded higher peak secretion rates and more defined pulsatility than pooled islets.
- The platform demonstrated ability to study compound effects on insulin secretion phases.
Conclusions:
- The novel platform provides a tool for studying dynamic insulin secretion at high temporal resolution and low variation.
- Single-islet perifusion offers a more physiologically relevant model for GSIS.
- This technology advances research into insulin secretion mechanisms and therapeutic interventions.
Abstract:
Insulin is released from pancreatic islets in a biphasic and pulsatile manner in response to elevated glucose levels. This highly dynamic insulin release can be studied in vitro with islet perifusion assays. Herein, a novel platform to perform glucose-stimulated insulin secretion (GSIS) assays with single islets is presented for studying the dynamics of insulin release at high temporal resolution. A standardized human islet model is developed and a microfluidic hanging-drop-based perifusion system is engineered, which facilitates rapid glucose switching, minimal sample dilution, low analyte dispersion, and short sampling intervals. Human islet microtissues feature robust and long-term glucose responsiveness and demonstrate reproducible dynamic GSIS with a prominent first phase and a sustained, pulsatile second phase. Perifusion of single islet microtissues produces a higher peak secretion rate, higher secretion during the first and second phases of insulin release, as well as more defined pulsations during the second phase in comparison to perifusion of pooled islets. The developed platform enables to study compound effects on both phases of insulin secretion as shown with two classes of insulin secretagogs. It provides a new tool for studying physiologically relevant dynamic insulin secretion at comparably low sample-to-sample variation and high temporal resolution.
