Fig. 6: Effect of β-cell-specific Tfeb KO on metabolic profile and target gene expression. | Nature Communications

Fig. 6: Effect of β-cell-specific Tfeb KO on metabolic profile and target gene expression.

From: Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress

Fig. 6

a GTT in Tfeb∆β-cell and TfebF/F mice on NCD or HFD for 12 weeks (left). AUC (right). b Insulinogenic index in Tfeb∆β-cell and TfebF/F mice on NCD or HFD for 12 weeks (left). Serum insulin levels before and 15 min after glucose injection (right). c mRNA from pancreatic islets of Tfeb∆β-cell and TfebF/F mice fed NCD or HFD for 12 weeks was subjected to real-time RT-PCR. d Pancreatic islets from NCD-fed Tfeb∆β-cell and TfebF/F mice were treated with mitochondrial stressors for 6 h. mRNA from the treated islets was subjected to real-time RT-PCR. (n = 8) e Expression of TFEB mRNA in 1.1B4 cells transfected with TFEB siRNA examined by real-time RT-PCR. (n = 6) f After treating TFEB siRNA-transfected 1.1B4 cells with mitochondrial stressors for 6 h, expression of the indicated genes was examined by real-time RT-PCR. (n = 6) (SiCon, control siRNA) g Forty-eight h after transfection of 1.1B4 cells with control GFP or TFEB-GFP, expression of the indicated genes was examined by real-time RT-PCR. (n = 4) h After treatment of 1.1B4 cells with mitochondrial stressors, ChIP assay was conducted. Fold changes (middle). Representative immunoblots (left). (n = 4) Positions of putative TFEB-binding CLEAR sequence in the promoter regions of NDP52 and OPTN (right). i Pancreatic islets from Nfe2l2-KO and control mice were treated with mitochondrial stressors for 6 h. Expression of Ndp52 and Optn evaluated by real-time RT-PCR mRNA. (n = 10 for Nfe2l2 WT; n = 12 for Nfe2l2 KO) All data in this figure are the means ± SEM from more than 3 independent experiments. P values were determined using o one-way ANOVA with Tukey’s test (a–d, f, h, i), two-way ANOVA with Bonferroni’s test (a) or two-tailed t test (e, g). ns, not significant; *, compared to (wild-type) cells or control transfectants treated with Veh; †, compared to wild-type cells or control transfectants treated with Rot alone; ‡, compared to wild-type cells or control transfectants treated with O/A alone.

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