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Updated: Aug 23, 2026
Isolated Pancreatic Islet Treatment and Apoptosis Measurement
Published on: May 2, 2025
Caspase-3 inhibitor prevents apoptosis of human islets immediately after isolation and improves islet graft function
Masahiko Nakano1, Ippei Matsumoto, Toshiya Sawada
1Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Objectives:
Apoptosis appears in islets after isolation, and it has a detrimental effect on the islet function. To improve the outcome of clinical islet transplantation, it is crucial to protect islets from apoptosis. The aim of this study was to determine whether a caspase-3 inhibitor (Z-DEVD-FMK) added to culture media protects islets from apoptosis and to compare the effects of fetal bovine serum (FBS) with human serum albumin (HSA) as a protein supplement in culture.
Methods:
Isolated human islets were cultured under 4 different conditions: 0.5% HSA (control), 0.5% HSA + 25 micromol/L Z-DEVD-FMK, 0.5% HSA + 100 micromol/L Z-DEVD-FMK and 10% FBS for 2 days. Next, 1000 IEQ islets precultured with 0.5% HSA and with or without 100 micromol/L Z-DEVD-FMK were transplanted to diabetic nude mice.
Results:
The islet yields were higher in Z-DEVD-FMK-treated groups, and the inhibitor prevented apoptosis dose dependently. The yield and insulin release were higher in FBS-treated group than in the control group, but FBS did not affect apoptosis. All 6 mice transplanted with islets pretreated with Z-DEVD-FMK, and 3 of 8 mice with control islets became normoglycemic posttransplantation.
Conclusion:
Z-DEVD-FMK prevented apoptosis of isolated human islets and improved its function. FBS (10%) improved the islet yield and insulin secretion more than 0.5% HSA.
Insights
A caspase-3 inhibitor, Z-DEVD-FMK, protected isolated human islets from apoptosis, improving transplant success. Fetal bovine serum (FBS) enhanced islet yield and insulin secretion compared to human serum albumin (HSA).
Area of Science:
- Endocrinology
- Immunology
- Cell Biology
Background:
- Islet cell apoptosis negatively impacts islet function and transplantation outcomes.
- Protecting islets from apoptosis is critical for successful islet transplantation.
Purpose of the Study:
- To evaluate the protective effect of a caspase-3 inhibitor (Z-DEVD-FMK) against apoptosis in isolated human islets.
- To compare the efficacy of fetal bovine serum (FBS) and human serum albumin (HSA) as protein supplements in islet culture media.
Main Methods:
- Human islets were cultured with varying concentrations of Z-DEVD-FMK and HSA, or with FBS.
- Islets pre-treated with Z-DEVD-FMK or HSA were transplanted into diabetic nude mice.
Main Results:
- Z-DEVD-FMK demonstrated a dose-dependent inhibition of islet apoptosis and improved islet yield.
- FBS supplementation increased islet yield and insulin release compared to HSA.
- Transplantation of Z-DEVD-FMK-treated islets resulted in a higher rate of normoglycemia in recipient mice.
Conclusions:
- Z-DEVD-FMK effectively prevents apoptosis in isolated human islets, enhancing their function and transplantation potential.
- FBS is a superior protein supplement to HSA for improving islet yield and insulin secretion in culture.
