Figure 2. Effect of IS5 on the kinetics of hIAPP fiber formation.
Representative traces showing the effect of IS5 on de novo fiber formation in solution (A), on solution phase fiber formation seeded with preformed fibers (B), on de novo fiber formation catalyzed by a lipid bilayer (C), and on IAPP induced cell toxicity (D). (A–C) Reactions were performed in the presence (filled) and absence (open) of compound (1:1 IS5:IAPP). De novo reactions contained 10µM hIAPP and 10 µM IS5. Seeded kinetics were performed at 20 µM hIAPP with the addition of 4 µM pre-formed IAPP fibers and 20 µM IS5. Lipid catalysis was performed by addition of 630 µM lipid in the form of a 1:1 mixture of DOPG:DOPC unilamellar liposomes. (D) Inhibition of hIAPP cell toxicity by IS5. INS-1 cells were treated with hIAPP (5 µM (gray) or 10 µM (black) ) and the indicated concentration of IS5. Cell viability was then assayed by MTT reduction (see methods). Results are expressed as percentages of the control cells exposed only to a matched volume of neat DMSO. All experiments performed at least in triplicate. For (D), error bars represent SEM. For (A–C), statistics are quoted in the main text.
