Fig 4: Active compounds protect human β-cells from glucolipotoxicity.

a. Overview of compounds included in cellular assays. Table shows results of cytotoxicity and β-cell rescue from glucolipotoxicity in the presence of the compounds (green indicates positive outcome and red cytotoxicity). b. Schematic of adaptation to the SPARKL assay in human islets to specifically monitor β-cells. c. Representative figures from d at 48 h with 43. The results are representative from 4 different human cadaveric donors. d. Representative kinetics of β-cell death in glucolipotoxicity (20 mM glucose+500 μM palmitate), in the presence of 10 μM of the indicated compounds. e. Quantification of β-cell death (assessed by Yoyo3+% of GFP+ cells) at 24 h from d. f. Human islets were treated for 24 h as indicated, followed by quantification of glucose-stimulated insulin secretion (GSIS) in KREBS buffer (2.8 mM glucose, 1% BSA) over 30 min. The corresponding GSIS-stimulation index (SI) was obtained by determining the ratio of insulin release at high vs low glucose. Data are means +/−SEM; n=4; p<0.01**, p<0.01; ***, p<0.005; ****, pP<0.001.