Conversely, the beneficial TMAO phenotype we observed in GLT cultured INS-1 β-cells and primary rat islets with 40 μM TMAO demonstrated normalized insulin secretion and content (Figure 2C,D,G,H), insulin granule density (Figure 3), and upregulated IRE1α UPR (Figure 5) relevant to the diet-induced T2D β-cell physiology (Graphical Abstract). The gene discussed is ERN1; the disease is type 2 diabetes mellitus.