To present a case of recurrent hypoglycemia following Roux-en-Y gastric bypass (RYGB) surgery whose etiology was determined to be a proinsulin-predominant pancreatic neuroendocrine tumor (a proinsulinoma).

The C-peptide of proinsulin is important for the biosynthesis of insulin, but has been considered for a long time to be biologically inert. Recent studies in diabetic patients have stimulated a new debate about its possible regulatory role, suggesting that it is a hormonally active peptide. We des-cribe structural studies of the C-peptide using 2D NMR spectroscopy.

We have investigated thein vitrorefolding process of human proinsulin (HPI) and an artificial mini-C derivative of HPI (porcine insulin precursor, PIP), and found that they have significantly different disulfide-formation pathways.HPI and PIP differ in their amino acid sequences due to the presence of the C-peptide linker found in HPI, therefore suggesting that the C-peptide linker may be responsible for the observed difference in folding behaviour.

The formation and structure of proinsulin C-peptide oligomers has been investigated by PAGE, NMR spectroscopy and dynamic light scattering. The results obtained show that C-peptide forms oligomers of different sizes, and that their formation and size distribution is altered by salt and divalent metal ions, which indicates that the aggregation process is medi-ated by electrostatic interactions.