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Sitagliptin promotes macrophage-to-faeces reverse cholesterol transport through reduced intestinal cholesterol absorption in obese insulin resistant CETP-apoB100 transgenic mice.
- Source :
-
Diabetes, obesity & metabolism [Diabetes Obes Metab] 2012 Jul; Vol. 14 (7), pp. 662-5. Date of Electronic Publication: 2012 Feb 13. - Publication Year :
- 2012
-
Abstract
- Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glycaemic control in type 2 diabetes, but their benefits on reverse cholesterol transport (RCT) remain unknown. We evaluated the effects of DPP-4i sitagliptin 500 mg/kg/day on RCT in obese insulin-resistant CETP-apoB100 transgenic mice. Metformin 300 mg/kg/day orally was used as a reference compound. Both metformin and sitagliptin showed the expected effects on glucose parameters. Although no significant effect was observed on total cholesterol and high-density lipoprotein (HDL) cholesterol levels, sitagliptin, but not metformin, increased faecal cholesterol mass excretion by 132% (p < 0.001 vs. vehicle), suggesting a potent effect on cholesterol metabolism. Mice were then injected i.p. with (3) H-cholesterol labelled macrophages to measure RCT over 48 h. Compared with vehicle, sitagliptin significantly increased macrophage-derived (3) H-cholesterol faecal excretion by 39%. Administration of (14) C-cholesterol labelled olive oil orally showed a significant reduction of (14) C-tracer plasma appearance over time with sitagliptin, indicating that this drug promotes RCT through reduced intestinal cholesterol absorption.<br /> (© 2012 Blackwell Publishing Ltd.)
- Subjects :
- Animals
Biological Transport drug effects
Biomarkers metabolism
Blood Glucose metabolism
Cholesterol metabolism
Cholesterol Ester Transfer Proteins metabolism
Diabetes Mellitus, Type 2 blood
Diabetes Mellitus, Type 2 drug therapy
Dipeptidyl-Peptidase IV Inhibitors pharmacology
Intestinal Absorption drug effects
Lipoproteins, HDL metabolism
Male
Mice
Mice, Obese
Mice, Transgenic
Sitagliptin Phosphate
Apolipoprotein B-100 pharmacology
Diabetes Mellitus, Type 2 metabolism
Hypoglycemic Agents pharmacology
Macrophages metabolism
Metformin pharmacology
Pyrazines pharmacology
Triazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1463-1326
- Volume :
- 14
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Diabetes, obesity & metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22268579
- Full Text :
- https://doi.org/10.1111/j.1463-1326.2012.01568.x