TY  - JOUR
AU  - Campbell, Scott A.
AU  - Hubert, Matthew
AU  - Johnson, Janyne
AU  - Salamon, Nicole
AU  - Light, Peter E.
PY  - 2019
DA  - 2019/06/26
TI  - The DPP4 Inhibitor Sitagliptin Increases Active GLP-1 Levels from Human Islets and May Increase Islet Cell Survival Prior to Transplantation
JO  - OBM Transplantation
SP  - 069
VL  - 03
IS  - 02
AB  - Background
One of the goals of clinical islet transplantation is to achieve a single-donor transplant that is dependent on obtaining enough quality  cell mass from one donor pancreas. Human islets are routinely cultured prior to transplantation, and pro-survival factors such as GLP-1 analogues have been reported to maintain  cell mass and survival. Interestingly, human islets may secrete GLP-1 and they also express the enzyme DPP4 that proteolytically cleaves GLP-1 into an inactive form. The aim of this study is to investigate GLP-1 secretion from human islets and to test if the DPP4 inhibitor sitagliptin may increase levels of active GLP-1 to increase islet survival in culture.
Methods
Active GLP-1, glucagon, and insulin were measured from non-diabetic and type 2 diabetic islets using a glucose suppression test. Human islet cultures were treated with sitagliptin, and active GLP-1 levels were taken at 48 hours. These levels were then correlated with islet isolation parameters (SI, viability, culture time, cold ischemia time, and DNA content) and donor parameters (age, HbA1c, and BMI). A dead cell assay using Sytox Green was used to measure cell death in human islet cultures treated with sitagliptin.
Results
We found that both non-diabetic and type 2 diabetic islets secrete active GLP-1. Active GLP-1 levels from human islets cultures negatively correlated with the stimulation index for insulin and this correlation was maintained when active GLP-1 levels were increased with sitagliptin. No strong correlations were found for other islet or donor parameters. The fold change in active GLP-1 in sitagliptin treated islet cultures was correlated with increased islet survival.
Conclusion
Human islets have a local paracrine source of the prosurvival peptide, active GLP-1. Although low levels of active GLP-1 are associated with greater  cell function, these levels may be increased with the DPP4 inhibitor sitagliptin. The increase in active GLP-1 levels may confer protection from islet cell death and pre-treatment of islets with DPP4 inhibitors prior to transplantation has the potential to improve post-transplant islet survival.
SN  - 2577-5820
UR  - https://doi.org/10.21926/obm.transplant.1902069
DO  - 10.21926/obm.transplant.1902069
ID  - Campbell2019
ER  -