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. 2016 Aug 5;5(10):807–822. doi: 10.1016/j.molmet.2016.07.009

Figure 7.

Figure 7

Inhibition of PDE's enhances the effect α-MSH on glucose disposal in DIO mice. A. Systemic α-MSH infusion did not increase glucose disposal in DIO mice (n = 8). B. Insulin and α-MSH-mediated glucose uptake was abrogated in ex vivo soleus extracted from DIO mice (n = 5). C. Systemic α-MSH infusion (1 μg/h) increases cAMP levels in muscles of lean mice instead of DIO mice (n = 5–7). cAMP concentration was measured after 45'of initiating α-MSH infusion and 25′ of starting GTT. D. α-MSH (100 nM) increases glucose uptake in differentiated L6-cells, and it is inhibited by pretreatment with a selective inhibitor of cAMP dependent protein kinase (15 μM H89 during 30′). ##p < 0.01 vs control, ***p < 0.001 vs H89. E. PDE4B expression in soleus muscle was higher in DIO mice than lean mice in basal conditions (n = 4–5). F. Quantification of PDE4B measured by Western blot as a ratio of β–actin (*p < 0.05 vs. lean). G. α-MSH (100 nM) increases glucose uptake in soleus muscles from DIO mice after a preincubation with a non-selective PDE inhibitor (Theophylline; 100 uM) for 20’. **p < 0.01 vs. basal baseline by one-way ANOVA followed by Bonferroni's Test. H. Pre-treatment with daily ip theophylline (20 mg/kg) for 5 days before systemic α-MSH infusion (1 μg/h) increases glucose disposal during ip GTT in DIO mice (n = 7). As a control, mice were pre-treated with the correspondent vehicle (DMSO 50%). ***p < 0.001 vs. Theophylline + α-MSH, £p < 0.05 and £££p < 0.001 vs. vehicle + α-MSH, #p < 0.05 and ##p < 0.01 vs. theophylline + saline by two-way ANOVA followed by Bonferroni's Test. I. Pre-treatment with ip Rolipram (5 mg/kg) two times daily for a period of 5 days before systemic α-MSH infusion (1 μg/h) increases glucose disposal during ip GTT in DIO mice (n = 8–9). It was compared to DIO mice receiving saline infusion. The systemic α-MSH infusion and posterior GTT was exactly as described in Figure 4. Data are expressed as mean ± SEM. *p < 0.05 and ***p < 0.001 vs. rolipram + α-MSH, £££p < 0.001 vs. vehicle + α-MSH, #p < 0.05 and ##p < 0.01 vs. rolipram + saline by two-way ANOVA followed by Bonferroni's Test.