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

Islet yield is a critical parameter to determine clinical use of isolated islets. Because islet equivalent (IEQ) is used to evaluate islet yield, it is important to know the function per IEQ. In this study, we assessed insulin secretion per IEQ by our newly developed single islet glucose-stimulated insulin release test (SI-GSIRT). For SI-GSIRT, an individual islet was classified by its diameter from the area of a digital image and calculated IEQ. Each single islet was incubated with low glucose followed by high glucose solutions. Insulin secretions by SI-GSIRT were compared based on diameter of islets. There was a significantly strong correlation between insulin secretion stimulated by high glucose solution and low glucose solution (R(2) =0.90, p< 0.001) confirming our technical applicability for SI-GSIRT. Insulin secretion stimulated by high glucose per IEQ was significantly lower in larger islets compared to smaller islets. This means that one IEQ from a large islet secretes less insulin than one IEQ from a small islet. In conclusion, we developed SI-GSIRT to evaluate single islets. This method revealed that large human islets secrete less insulin per IEQ. Thus the distribution of islet size must be monitored when the glucose stimulation test is conducted.