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

The aim of this study was to investigate the effects of the type-4 dipeptidyl peptidase (DPP-4) inhibitors linagliptin and vildagliptin as well as the sulfonylurea glimepiride on endothelium-dependent relaxation of aortae from female db/db mice with established hyperglycemia to determine whether the...

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Bibliographic Details
Published in:Diabetes, metabolic syndrome and obesity metabolic syndrome and obesity, 2019-08, Vol.12, p.1449-1458
Main Authors: Woodman, Owen L, Ortega, Jacinta M, Hart, Joanne L, Klein, Thomas, Potocnik, Simon
Format: Article
Language:English
Subjects:
Acetylcholine
Analysis
Animals
Antioxidants
Antioxidants (Nutrients)
Arginine
Carbon dioxide
Coronary vessels
Diabetes
Diabetes therapy
DPP-4 inhibitor
Endothelium
endothelium-dependent relaxation
Glimepiride
Glucose
Hyperglycemia
Hypoglycemic agents
linagliptin
Nitric oxide
Nitrogen oxides
Original Research
Oxidative stress
reactive oxygen species
Sitagliptin
Sulfonylureas
Superoxides
Type 2 diabetes
Veins & arteries
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Summary:The aim of this study was to investigate the effects of the type-4 dipeptidyl peptidase (DPP-4) inhibitors linagliptin and vildagliptin as well as the sulfonylurea glimepiride on endothelium-dependent relaxation of aortae from female db/db mice with established hyperglycemia to determine whether these treatments were able to attenuate diabetes-induced endothelial dysfunction. The mice were treated with glimepiride (2 mg/kg po per day, weeks 1-6, n=12), glimepiride plus vildagliptin (glimepiride 2 mg/kg po per day, weeks 1-6; vildagliptin 3 mg/kg po per day, weeks 4-6, n=11), glimepiride plus linagliptin (glimepiride 2 mg/kg po per day, weeks 1-6; linagliptin 3 mg/kg po per day, weeks 4-6, n=11) or linagliptin (3 mg/kg po per day, weeks 1-6, n=12). Endothelium-dependent relaxation using acetylcholine was assessed in the absence and presence of pharmacological tools (TRAM-34 1 μM; apamin 1 μM; N-nitro-L-arginine [L-NNA] 100 μM; 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one [ODQ] 10 μM) to distinguish relaxation mediated by nitric oxide (NO). Linagliptin was associated with a significant improvement in endothelium-dependent relaxation (ACh Rmax; db/db 41±1%, linagliptin 73±6%,
ISSN:1178-7007
1178-7007
DOI:10.2147/DMSO.S215086