Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice
Figure 6
Insulin sensitivity and signaling after treatment with selective inhibitors.
Glucose uptake obtained by the euglycaemic hyperinsulinaemic clamp from TLR2−/− mice treated or not with the drugs: SP600125 (SP), JNK inhibitor; 4-phenil butyric acid (PBA), endoplasmic reticulum stress inhibitor; TLR4 antisense oligonucleotide (ASO); (A) TAK-242, inhibitor of TLR4. (B) Serine phosphorylation of AKT after the treatment with SP600125 and PBA. (C) Serine phosphorylation of AKT after the treatment with TLR4 ASO and TAK-242. (D) Phosphorylation of JNK after the treatment with the drugs mentioned. Fasted TLR2 knockout mice and WT mice were gavaged by LPS (1.08, 10−8 g) diluted in water (100 µL) or without LPS. (E) Blood was collected from the cava vein 60 min after gavage and serum LPS was determined. (F) Zonula occludens (ZO)-1 expression in the ileum. (G) Frequency of CD4+Foxp3+ regulatory T cells in WT mice. (H) Frequency of CD4+Foxp3+ regulatory T cells in TLR2−/− mice. All evaluations were made with mice on standard chow. Data are presented as means ± S.E.M from six to eight mice per group from experiments that were repeated at least three times. * p<0.05 between WT mice with or without insulin stimulus; ** p<0.05 between WT and TLR2−/− mice with insulin stimulus ; $ p<0.05 between TLR2−/− mice with insulin stimulus, treated or not with SP; # p<0.05 between TLR2−/− mice with insulin stimulus, treated or not with PBA; § p<0.05 between TLR2−/− mice with insulin stimulus, treated or not with ASO; & p<0.05 between TLR2−/− mice with insulin stimulus, treated or not with TAK-242; a p<0.05 between WT mice with or without LPS stimulus; ° p<0.05 between WT and TLR2−/− mice with LPS stimulus.