How pancreatic beta cells lose their protein-folding helpers

Inside each insulin-producing beta cell, a small team of helper proteins does the work of folding the insulin precursor proinsulin into its working shape. The team is anchored by BiP (binding immunoglobulin protein) and a set of partner proteins called cochaperones. A PNAS study from Randal Kaufman's lab at Sanford Burnham Prebys, with the University of Michigan, names that team for the first time and shows what happens when a key member is missing: misfolded proinsulin piles up, the cell comes under endoplasmic reticulum stress (a state of accumulated unfolded or misfolded proteins), and insulin output drops.

The finding, published June 1, 2026, builds on earlier work that had established misfolded proinsulin accumulates in diabetes but had not identified the helper proteins that coordinate folding. Senior and corresponding author Randal J. Kaufman, PhD, is a professor in the Center for Metabolic and Liver Diseases at Sanford Burnham Prebys.

Strengthening this folding machinery is a candidate way to protect beta cells as diabetes progresses, not a new treatment, and the standard of care (insulin replacement and glycemic control) is unchanged by the result. The chaperone network is one of several stress pathways eroding beta cells, and protein-folding targets in diabetes have been pursued before without clinical payoff.

What remains unknown: whether any of the named cochaperones has an existing drug candidate, in any indication, that could be repurposed. Without that, the work stays in basic-science territory.