Fig. 3.

AdiporonPEG₅ reduces β-cell ceramide species and promotes expression of β-cell identity genes in the presence of palmitate. A: De novo synthesis of sphingolipids begins with the condensation of serine and palmitate to 3-ketosphinganine, which is reduced to sphinganine. Ceramide synthase catalyzes the N-acylation of sphinganine to dihydro-ceramide, which forms ceramide after desaturation. B and C: Changes in the cellular levels of dihydro-ceramide (B) and ceramides (C) in response to drug treatment. INS1 cells treated with palmitate (0.25 mM) and drugs for 24 h were assayed for their ceramide levels by mass spectrometry. Changes in the lipid level were normalized against control cells treated with palmitate. D and E: Relative gene expressions of insulin secretion related genes in INS-1 cells treated with AdipoRon or AdipoRonPEG₅ (both 20 μM) in the absence of palmitate (D) or in the presence of palmitate (E) (n = 6). Data are mean ± SEM. ∗P < 0.05, ∗∗P < 0.01 and ∗∗∗P < 0.001.