Figure 5 |. Pyruvate carboxylase supports aspartate and ureagenesis, and is required for the protective effects of glucose metabolism.

a, M+3 malate levels in mouse islets labeled with ¹³C₆ glucose and treated as in Fig. 4c. Data are pooled means from n=5 (Veh, RO0281675), n=6 (BAD SAHB_A SD) and n=5 (BAD SAHB_A AAA) independent experiments.

b–c, The effect of PC knockdown on urea and NO (b) and aspartate levels (c) in human islets treated with cytokines in the context of protective glucose metabolism, n=3 human donors in b, and n=3 independent experiments from one donor in c.

d, The effect of PC knockdown on viability of human islets treated as in (b). On-target effects of knockdown were validated by rescue with an shRNA-resistant human PC cDNA compared to vector control (VC), n=3 donors.

e, The effect of PC inhibition by PAA on the viability of human islets treated with cytokines in the context of protective glucose metabolism, n=4 donors.

f, GLS activity is not required for the protective effects of glucose metabolism. Viability of BAD SAHB_A SD-treated human islets exposed to inflammatory cytokines in the absence or presence of BPTES for 48 h, n=3 donors.

Data are means ± s.e.m. from independent experiments with statistical analyses using one-way ANOVA with Tukey adjustment for multiple comparisons.