Fig. 9.

Reduction of insulin by TXNL1 prevents insulin fibril formation. On top of the figure a scheme is shown illustrating how oxidized insulin can be present as either hexamer, dimer or monomer (PDB structures visualized with the PyMol software using structures 3AIY, 6S34, 3I40 and 5E7W). When the disulfides in insulin become reduced, the A and B chains separate and then easily precipitate, thereby easily forming protofibrils, fibrils or amyloid. Here we evaluated the insulin reduction products using TEM upon either reduction using (A) 0.5 mM DTT, or enzymatically with either (B) NADPH + TrxR1 + Trx1 or (C) NADPH + TrxR1 + TXNL1, with the TEM images shown at two different degrees of magnification (see scale bar inserts). See text for further details.