A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay

Abstract

IntroductionStatic incubation (static glucose-stimulated insulin secretion, sGSIS) is a measure of islet secretory function. The Stimulation Index (SI; insulin produced in high glucose/insulin produced in low glucose) is currently used as a product release criterion of islet transplant potency.Research design and methodsOur hypothesis was that the Delta, insulin secreted in high glucose minus insulin secreted in low glucose, would be more predictive. To evaluate this hypothesis, sGSIS was performed on 32 consecutive human islet preparations, immobilizing the islets in a slurry of Sepharose beads to minimize mechanical perturbation. Simultaneous full-mass subrenal capsular transplants were performed in chemically induced diabetic immunodeficient mice. Logistic regression analysis was used to determine optimal cut-points for diabetes reversal time and the Fisher Exact Test was used to assess the ability of the Delta and the SI to accurately classify transplant outcomes. Receiver operating characteristic curve analysis was performed on cut-point grouped data, assessing the predictive power and optimal cut-point for each sGSIS potency metric. Finally, standard Kaplan-Meier-type survival analysis was conducted.ResultsIn the case of the sGSIS the Delta provided a superior islet potency metric relative to the SI.ConclusionsThe sGSIS Delta value is predicitive of time to diabetes reversal in the full mass human islet transplant bioassay.

Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling

“…GSIS analysis in week 2 of stage 6 is the most common timepoint selected for quality assessment in use of SC-islets differentiation protocols (Mahaddalkar et al, 2020;Hogrebe et al, 2021;Balboa et al, 2022). Although under debate, the SI > 1, determined from the ratio of insulin produced in high-and low-glucose, is currently a fundamental release criterion for human islets transplantation (Glieberman et al, 2021;Molano et al, 2024). That said, our data supported that the SC-islets can be used for downstream Frontiers in Bioengineering and Biotechnology frontiersin.org application in a 6-week time window (from weeks 2-8 of stage 6) without significant abnormality in GSIS ability.…”