Influence of type-4 dipeptidyl peptidase inhibition on endothelium-dependent relaxation of aortae from a db/db mouse model of type 2 diabetes: a comparison with the effect of glimepiride

Figures

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  Figure 1. Body weights (A), blood glucose concentration (B) and HbA1c (C) in the six different groups of mice over the 6-week treatment period. All parameters were significantly higher in db/db compared to C57/BL6 mice and none of the treatments had any effect. Data are expressed as means ± standard error (SEM). #p<0.001 compared to db/db over the 6-week treatment period, two-way ANOVA and Dunnett’s test, n=10–12. Abbreviation: ANOVA, analysis of variance.

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  Figure 2. The plasma concentration of glucagon-like peptide 1 (GLP-1) was significantly lower in C57/BL6 compared to db/db mice. GLP-1 concentration was not affected by any of the treatments. Data are expressed as mean ± SEM. #Significantly different compared to C57/BL6 (veh), p<0.05 one-way ANOVA and Sidak’s test, n=10–12. Abbreviation: ANOVA, analysis of variance.

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  Figure 3. Measurement of superoxide generated in mouse aortae using L-012 enhanced chemiluminescence from the six groups. Data are expressed as mean ± SEM. Notes: $Significantly different to C57/BL6 (veh), p<0.05, one-way ANOVA, Sidak’s multiple comparisons test. #Significantly different to db/db, p<0.05, one-way ANOVA, Sidak’s multiple comparisons test. *Significantly different to db/db (veh) and db/db + glimepiride, p<0.05, one-way ANOVA, Sidak’s multiple comparisons test. n=10–12. Abbreviation: ANOVA, analysis of variance.

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  Figure 4. Concentration response curves to ACh aortae from C57/BL6 mice and db/db mice treated with vehicle, glimepiride or linagliptin for 6 weeks. Responses to ACh were tested in the absence (A) or presence of TRAM-34 plus apamin (B) to inhibit IKCa and SKCa, respectively, or N-nitro L-arginine (L-NNA) plus 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (C) to block nitric oxide synthase and guanylate cyclase, respectively. Calculated values for sensitivity (pEC50) and maximum response (Rmax) derived from these data are shown in Table 1.

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  Figure 5. Concentration response curves to ACh in aortae from C57/BL6 mice and db/db mice treated with vehicle or glimepiride either alone or in combination with vildagliptin or linagliptin. Responses to ACh were tested in the absence (A) or presence of TRAM-34 plus apamin (B) to inhibit IKCa and SKCa, respectively, or N-nitro L-arginine (L-NNA) plus 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (C) to block nitric oxide synthase and guanylate cyclase, respectively. Calculated values for sensitivity (pEC50) and maximum response (Rmax) derived from these data are shown in Table 1.