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Author Spotlight: Investigating Islet Abnormalities and Function with a Pseudoislet Protocol
Published on: November 3, 2023
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Integrated human pseudoislet system and microfluidic platform demonstrate differences in GPCR signaling in islet
John T Walker1, Rachana Haliyur1, Heather A Nelson2
1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
JCI Insight
|May 1, 2020
Summary
Researchers developed a new method to study human islet cells, revealing how specific signaling pathways affect insulin and glucagon secretion, offering insights into diabetes.
Area of Science:
- Endocrinology
- Cell Biology
- Diabetes Research
Background:
- Pancreatic islets regulate blood glucose via insulin and glucagon secretion.
- Dysregulated hormone secretion from islet cells is central to diabetes.
- Studying islet cell signaling is challenging due to their complex 3D structure.
Purpose of the Study:
- To develop an integrated approach for studying primary human islet cell function.
- To investigate the roles of Gi and Gq GPCR pathways in regulating insulin and glucagon secretion.
- To understand intracellular signaling dynamics and hormone secretion in human β and α cells.
Main Methods:
- Genetically engineered pseudoislets mimicking native islet architecture.
- Microperifusion system for simultaneous biosensor signal and hormone secretion measurement.
- Designer receptors exclusively activated by designer drugs (DREADDs) to modulate GPCR signaling.
Main Results:
- Gi GPCR pathway activation reduced both insulin and glucagon secretion.
- Gq GPCR pathway activation stimulated glucagon secretion.
- Gq pathway had mixed effects on insulin secretion, linked to intracellular Ca2+ changes.
- Demonstrated distinct GPCR signaling differences between human β and α cells.
Conclusions:
- The combined pseudoislet and microfluidic system enables coregistration of signaling and secretion.
- This approach provides novel insights into human islet cell function and GPCR signaling.
- Findings contribute to understanding islet dysfunction in diabetes.
