Abstract | AIM: METHODS: RESULTS:
Vildagliptin increased plasma GLP-1 and GIP levels without affecting food intake, body weight, blood pressure, or plasma lipid profile in any of the animals tested, though it reduced HbA1c in the diabetic mice. Diabetic Apoe (-/-) mice exhibited further-progressed atherosclerotic lesions and foam cell formation compared with nondiabetic counterparts. Nondiabetic and diabetic Apoe (-/-) mice showed a comparable response to vildagliptin, namely, remarkable suppression of atherosclerotic lesions with macrophage accumulation and foam cell formation in peritoneal macrophages. Exendin(9-39) or ( Pro(3))GIP partially attenuated the vildagliptin-induced suppression of atherosclerosis. The two blockers in combination abolished the anti-atherosclerotic effect of vildagliptin in nondiabetic mice but only partly attenuated it in diabetic mice. Vildagliptin suppressed macrophage foam cell formation in nondiabetic and diabetic mice, and this suppressive effect was abolished by infusions with exendin(9-39)+( Pro(3))GIP. Incubation of DPP-4 or vildagliptin in vitro had no effect on macrophage foam cell formation. CONCLUSIONS:
Vildagliptin confers a substantial anti-atherosclerotic effect in both nondiabetic and diabetic mice, mainly via the action of the two incretins. However, the partial attenuation of atherosclerotic lesions by the dual incretin receptor antagonists in diabetic mice implies that vildagliptin confers a partial anti-atherogenic effect beyond that from the incretins.
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Authors | Michishige Terasaki, Masaharu Nagashima, Kyoko Nohtomi, Kyoko Kohashi, Masako Tomoyasu, Kyoko Sinmura, Yukinori Nogi, Yuki Katayama, Kengo Sato, Fumiko Itoh, Takuya Watanabe, Tsutomu Hirano |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 8
Pg. e70933
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23967137
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apolipoproteins E
- Dipeptidyl-Peptidase IV Inhibitors
- Glp1r protein, mouse
- Glucagon-Like Peptide-1 Receptor
- Incretins
- Nitriles
- Pyrrolidines
- Receptors, Glucagon
- Dipeptidyl Peptidase 4
- Vildagliptin
- Adamantane
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Topics |
- Adamantane
(analogs & derivatives, pharmacology)
- Alternative Splicing
- Animals
- Apolipoproteins E
(genetics)
- Atherosclerosis
(genetics, metabolism, pathology, prevention & control)
- Dipeptidyl Peptidase 4
(metabolism)
- Dipeptidyl-Peptidase IV Inhibitors
(pharmacology)
- Disease Models, Animal
- Foam Cells
(metabolism, pathology)
- Gene Expression Profiling
- Gene Expression Regulation
- Gene Order
- Glucagon-Like Peptide-1 Receptor
- Glucose Tolerance Test
- Incretins
(metabolism)
- Macrophages
(metabolism, pathology)
- Male
- Mice
- Mice, Inbred NOD
- Mice, Knockout
- Nitriles
(pharmacology)
- Pyrrolidines
(pharmacology)
- Receptors, Glucagon
(antagonists & inhibitors, genetics, metabolism)
- Vildagliptin
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