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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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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.

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|November 18, 2025
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Summary

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.

Keywords:
GSISinsulin secretionislet transplantationperifusion

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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.