SYVN1 and diabetes mellitus: We find that, beyond the islet cell heterogeneity appearing in the islets of β-Hrd1-KO mice that consistently develop hypoinsulinemic diabetes, there is a notable increase in the phosphorylation state of eIF2α, which is known to limit proinsulin biosynthesis, as well as an activation of autophagy that participates in proinsulin turnover.