title: Sitagliptin prevents the development of metabolic and hormonal disturbances, increased β-cell apoptosis and liver steatosis induced by a fructose-rich diet in normal rats.
abstract: The aim of the present study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, β-cell mass decrease and hepatic steatosis induced by F (fructose) in rats. Normal adult male Wistar rats received a standard commercial diet without (C) or with 10% (w/v) F in the drinking water (F) for 3 weeks; animals from each group were randomly divided into three subgroups: untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS; 115.2 mg/day per rat) or exendin-4 (CE and FE; 0.35 nmol/kg of body weight, intraperitoneally). Water and food intake, oral glucose tolerance, plasma glucose, triacylglycerol (triglyceride), insulin and fructosamine concentration, HOMA-IR [HOMA (homoeostasis model assessment) for insulin resistance], HOMA-β (HOMA for β-cell function) and liver triacylglycerol content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose tolerance), plasma triacylglycerol, fructosamine and insulin levels, HOMA-IR and HOMA-β indexes, and liver triacylglycerol content were significantly higher in F rats. Islet β-cell mass was significantly lower in these rats, due to an increase in the percentage of apoptosis. The administration of exendin-4 and sitagliptin to F animals prevented the development of all the metabolic disturbances and the changes in β-cell mass and fatty liver. Thus these compounds, useful in treating Type 2 diabetes, would also prevent/delay the progression of early metabolic and tissue markers of this disease.
authors.affiliation: CENEXA - Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET LA PLATA, Centro Colaborador OPS/OMS), Facultad de Ciencias Médicas UNLP, La Plata, Argentina.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Maiztegui
authors.forename: María I
authors.initials: MI
authors.lastname: Borelli
authors.forename: Viviana G
authors.initials: VG
authors.lastname: Madrid
authors.forename: Héctor
authors.initials: H
authors.lastname: Del Zotto
authors.forename: María A
authors.initials: MA
authors.lastname: Raschia
authors.forename: Flavio
authors.initials: F
authors.lastname: Francini
authors.forename: María L
authors.initials: ML
authors.lastname: Massa
authors.forename: Luis E
authors.initials: LE
authors.lastname: Flores
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Rebolledo
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gagliardino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004326:Drinking / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004435:Eating / Q000187:drug effects; D000077270:Exenatide; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005632:Fructose / Q000008:administration & dosage; D005951:Glucose Tolerance Test / Q000379:methods; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000473:pathology / Q000517:prevention & control*; D010455:Peptides / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*; D014688:Venoms / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010455:Peptides; D011719:Pyrazines; D014230:Triazoles; D014688:Venoms; D005632:Fructose; D000077270:Exenatide; D000068900:Sitagliptin Phosphate