Sitagliptin promotes macrophage-to-faeces reverse cholesterol transport through reduced intestinal cholesterol absorption in obese insulin resistant CETP-apoB100 transgenic mice

Autor: François Briand, T. Sulpice, Quentin Thieblemont, Rémy Burcelin
Přispěvatelé: Physiogenex, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise
Rok vydání: 2012
Předmět:
Blood Glucose
Male
Endocrinology
Diabetes and Metabolism
Mice
Obese
Type 2 diabetes
MESH: Metformin
MESH: Lipoproteins
HDL
chemistry.chemical_compound
Mice
0302 clinical medicine
Endocrinology
MESH: Cholesterol
MESH: Animals
MESH: Mice
Obese
0303 health sciences
MESH: Dipeptidyl-Peptidase IV Inhibitors
Reverse cholesterol transport
Metformin
3. Good health
Cholesterol
MESH: Cholesterol Ester Transfer Proteins
Sitagliptin
MESH: Pyrazines
Pyrazines
Apolipoprotein B-100
Intestinal cholesterol absorption
lipids (amino acids
peptides
and proteins)
Lipoproteins
HDL
medicine.drug
MESH: Diabetes Mellitus
Type 2
medicine.medical_specialty
MESH: Mice
Transgenic
MESH: Intestinal Absorption
MESH: Biological Transport
030209 endocrinology & metabolism
Mice
Transgenic
Sitagliptin Phosphate
03 medical and health sciences
Internal medicine
MESH: Hypoglycemic Agents
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Internal Medicine
medicine
Animals
Hypoglycemic Agents
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
MESH: Mice
030304 developmental biology
MESH: Apolipoprotein B-100
Dipeptidyl-Peptidase IV Inhibitors
business.industry
Macrophages
MESH: Biological Markers
MESH: Macrophages
Biological Transport
Triazoles
medicine.disease
MESH: Male
Cholesterol Ester Transfer Proteins
chemistry
MESH: Triazoles
Diabetes Mellitus
Type 2
Intestinal Absorption
MESH: Blood Glucose
business
Biomarkers
Lipoprotein
Zdroj: Diabetes, Obesity and Metabolism
Diabetes, Obesity and Metabolism, Wiley, 2012, 14 (7), pp.662-5. ⟨10.1111/j.1463-1326.2012.01568.x⟩
Diabetes, Obesity and Metabolism, 2012, 14 (7), pp.662-5. ⟨10.1111/j.1463-1326.2012.01568.x⟩
ISSN: 1463-1326
1462-8902
DOI: 10.1111/j.1463-1326.2012.01568.x⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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