Dipeptidyl peptidase 4 inhibitor improves brain insulin sensitivity, but fails to prevent cognitive impairment in orchiectomy obese rats

1. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 1

   The experimental protocol of the present study.
2. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 2

   The effects of vildagliptin on brain insulin receptor (IR) function, including insulin-induced LTD, the phosphorylation of IR (p-IR) and the expression of IRs in testosterone-deprived rats with or without obesity. Insulin-induced LTD in the CA1 hippocampus and the p-IR significantly decreased in HFOV rats, when compared with that of NDS rats (A and B). The administration of vildagliptin for 4 weeks significantly improved the ability of insulin-induced LTD and the p-IR in HFOVil rats, when compared with that of HFOV rats (A and B). No differences in the expression of IR among all groups were found (C). NDS, sham-operated rats with normal diet feeding; NDOV, orchiectomized-operated rats with normal diet feeding and treated with vehicle; NDOVil, orchiectomized-operated rats with normal diet feeding and treated with vildagliptin; HFOV, orchiectomized-operated rats with high-fat diet feeding and treated with vehicle; HFOVil, orchiectomized-operated rats fed with a high-fat diet and treated with vildagliptin. *P<0.05 vs NDS and ^†P<0.05 vs HFOV. A full colour version of this figure is available at http://dx.doi.org/10.1530/JOE-15-0099.
3. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 3

   The effects of vildagliptin on brain mitochondrial function in testosterone deprived rats with or without obesity. HFOV rats demonstrated brain mitochondrial dysfunction, as indicated by increased brain mitochondrial ROS production following H₂O₂ application (A), increased brain mitochondrial membrane potential (ΔΨm) change following H₂O₂ application (B) and decreased absorbance values, indicating brain mitochondrial swelling (C). The administration of vildagliptin for 4 weeks significantly decreased brain mitochondrial ROS production in HFOVil rats, when compared with that of HFOV rats (A). However, vildagliptin did not improve brain ΔΨm change and brain mitochondrial swelling in HFOVil rats (B and C). NDS, sham-operated rats with normal diet feeding; NDOV, orchiectomized-operated rats with normal diet feeding and treated with vehicle; NDOVil, orchiectomized-operated rats with normal diet feeding and treated with vildagliptin; HFOV, orchiectomized-operated rats with high-fat diet feeding and treated with vehicle; HFOVil, orchiectomized-operated rats with high-fat diet feeding and treated with vildagliptin. *P<0.05 vs NDOV and ^†P<0.05 vs HFOV.
4. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 4

   Representative images of brain mitochondrial morphology by transmission electron microscopy (JEM-2200FS field emission electron microscope, original magnification ×20 000) after 4 weeks of vildagliptin treatment. Normal folding of cristae in brain mitochondrial morphology was shown among all normal diet-fed rats (A, B and C). However, brain mitochondrial swelling, as indicated by unfolded cristae, of both HFOV and HFOVil groups was observed (D and E). NDS, sham-operated rats with normal diet feeding; NDOV, orchiectomized-operated rats with normal diet feeding and treated with vehicle; NDOVil, orchiectomized-operated rats with normal diet feeding and treated with vildagliptin; HFOV, orchiectomized-operated rats with high-fat diet feeding and treated with vehicle; HFOVil, orchiectomized-operated rats with high-fat diet feeding and treated with vildagliptin.
5. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 5

   The effects of vildagliptin on hippocampal synaptic long-term potentiation (LTP) and the cognitive function determined by Morris water maze (MWM) test in testosterone-deprived rats with or without obesity. Both orchiectomized-operated groups (NDOV and HFOV rats) significantly reduced the percentage of normalized fEPSPs, when compared with that of NDS rats (A). The administration of vildagliptin for 4 weeks did not improve the percentage of normalized fEPSPs in both orchiectomized-operated groups (NDOVil and HFOVil), when compared with that of HFOV rats (A). HFOV rats and HFOVil rats significantly increased time to reach the platform in the acquisition test as well as had a decreased time spent in target quadrant in the probe test, when compared with that of NDS rats (B and C). NDOV rats had a significantly decreased time spent in the target quadrant in the probe test, but there was no changed in time to reach the platform in the acquisition test (B and C). The administration of vildagliptin for 4 weeks did not restore the time taken to reach the platform in HFOVil rats, and the time spent in the target quadrant in both NDOVil and HFOVil rats (B and C). NDS, sham-operated rats with normal diet feeding; NDOV, orchiectomized-operated rats with normal diet feeding and treated with vehicle; NDOVil, orchiectomized-operated rats with normal diet feeding and treated with vildagliptin; HFOV, orchiectomized-operated rats with high-fat diet feeding and treated with vehicle; HFOVil, orchiectomized-operated rats with high-fat diet feeding and treated with vildagliptin; HFS, high frequency stimulation. *P<0.05 vs NDS.

• © 2015 Society for Endocrinology