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Updated: Jan 11, 2026
Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
Published on: May 10, 2018
Standardized dynamic glucose testing reveals donor-dependent heterogeneity in human islet function
Priyadarshini Gnanasekar1, Chiara Saponaro1, Markus Mühlemann1
1Inserm U1190, CHU Lille, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Univ. Lille, Lille, France.
Insights
Dynamic perifusion better reveals glucose-stimulated insulin secretion (GSIS) heterogeneity in human islets compared to static methods. Donor BMI and HbA1c significantly impact insulin secretion patterns, highlighting key factors in beta-cell function variability.
Area of Science:
- Endocrinology
- Metabolic Research
- Islet Biology
Background:
- Glucose-stimulated insulin secretion (GSIS) is vital for assessing pancreatic beta-cell function.
- Variability in GSIS testing protocols complicates the interpretation of beta-cell function across individuals.
Purpose of the Study:
- To investigate insulin secretion heterogeneity in human islets from 576 donors.
- To compare static incubation and dynamic perifusion techniques for GSIS assessment.
- To examine the influence of donor characteristics on insulin secretory responses.
Main Methods:
- Compared static incubation (n=408) and dynamic perifusion (n=168) using standardized glucose concentrations (3 vs 15 mM).
- Analyzed insulin secretion patterns, stimulation indices, and temporal responses.
- Utilized cluster analysis to identify donor groups based on age, BMI/BSA, and HbA1c.
Main Results:
- Dynamic perifusion captured temporal secretion patterns and a greater dynamic range compared to static incubation.
- Insulin content normalization in perifusion revealed a 22-fold variation in stimulation index across donors.
- Donor BMI and HbA1c significantly influenced basal insulin secretion, especially in individuals with glucose intolerance or type 2 diabetes (T2D).
- Cluster analysis identified two distinct donor groups based on age, BMI/BSA, and HbA1c that predicted insulin secretion patterns; donor sex had no impact.
Conclusions:
- Standardized dynamic perifusion is superior to static incubation for resolving islet glucose responses and revealing significant donor heterogeneity.
- Donor characteristics, particularly BMI and HbA1c, are primary drivers of variability in insulin secretion profiles.
- Understanding this heterogeneity is crucial for accurate beta-cell function assessment and T2D research.
Abstract:
Glucose-stimulated insulin secretion (GSIS) testing of isolated islets of Langerhans is crucial for assessing β-cell function, yet protocol variability complicates result interpretation. This study investigated insulin secretion heterogeneity across 576 donors and examined the influence of donor characteristics on secretory responses. We compared static incubation (n = 408) and dynamic perifusion (n = 168) techniques using standardized glucose stimulation protocols (3 vs 15 mM). While both methods showed comparable stimulation indices (r2 = 0.652), dynamic perifusion uniquely captured temporal secretion patterns and revealed greater dynamic range in insulin responses. Notably, dynamic perifusion, with insulin content normalization, revealed a 22-fold variation in stimulation index across donors. Body mass index (BMI) and HbA1c significantly influenced basal insulin secretion, particularly in donors with glucose intolerance and type 2 diabetes (T2D) (HbA1c ≥ 6.5%). Cluster analysis identified two distinct groups based on age, BMI/body surface area (BSA), and HbA1c, which strongly predicted insulin secretion patterns, whereas donor sex had no measurable impact. This large-scale study demonstrates the superiority of standardized perifusion over static incubation for resolving islet glucose responses. By capturing dynamic secretion profiles, perifusion reveals substantial donor heterogeneity, primarily driven by BMI and HbA1c through their effects on basal insulin secretion.
