Large human islets secrete less insulin per islet equivalent than smaller islets in vitro

Area of Science:

• Endocrinology
• Islet Biology
• Diabetes Research

Background:

• Islet yield is crucial for clinical applications of isolated islets.
• Islet Equivalent (IEQ) is a standard metric, but its functional capacity varies.
• Assessing function per IEQ is vital for accurate islet yield evaluation.

Purpose of the Study:

• To develop and validate a novel method for assessing insulin secretion from individual islets.
• To determine the relationship between islet size and insulin secretion per IEQ.
• To evaluate the functional capacity of islets based on their size distribution.

Main Methods:

• Development of a Single Islet Glucose-Stimulated Insulin Release Test (SI-GSIRT).
• Classification of individual islets by diameter using digital imaging to calculate IEQ.
• Incubation of single islets with sequential low and high glucose solutions to measure insulin secretion.
• Statistical analysis of insulin secretion data correlated with islet size and IEQ.

Main Results:

• SI-GSIRT demonstrated high technical applicability with a strong correlation between insulin secretion under different glucose conditions (R²=0.90, p<0.001).
• Insulin secretion per IEQ was significantly lower in larger islets compared to smaller islets when stimulated by high glucose.
• This indicates that larger islets have a reduced functional capacity on a per-IEQ basis.

Conclusions:

• The developed SI-GSIRT is a reliable method for evaluating single islet function.
• Human islets exhibit size-dependent differences in insulin secretion per IEQ, with larger islets being less efficient.
• Islet size distribution should be considered during glucose stimulation tests for accurate islet yield assessment in clinical settings.