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
Autor: | Viviana Graciela Madrid, Bárbara Maiztegui, Oscar R. Rebolledo, M. A. Raschia, Flavio Francini, Hector Herminio del Zotto, Luis Emilio Flores, María Laura Massa, Juan José Gagliardino, M I Borelli |
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Rok vydání: | 2010 |
Předmět: |
Blood Glucose
Male medicine.medical_treatment Drug Evaluation Preclinical Apoptosis Impaired glucose tolerance Eating Insulin-Secreting Cells Metabolic Syndrome Fatty liver Metabolic disorder Otras Medicina Básica General Medicine Medicina Básica Sitagliptin Pyrazines hormones hormone substitutes and hormone antagonists INSULIN RESISTANCE medicine.drug medicine.medical_specialty SITAGLIPTIN CIENCIAS MÉDICAS Y DE LA SALUD Drinking Fructose Biology Sitagliptin Phosphate Insulin resistance Internal medicine medicine PRE-DIABETES Animals Hypoglycemic Agents Rats Wistar EXENDIN-4 Dipeptidyl-Peptidase IV Inhibitors Venoms Insulin Body Weight β-CELL MASS nutritional and metabolic diseases Glucose Tolerance Test Triazoles medicine.disease Diet Rats Fatty Liver Endocrinology HYPERTRIGLYCERIDAEMIA Exenatide Steatosis Peptides |
Zdroj: | Clinical science (London, England : 1979). 120(2) |
ISSN: | 1470-8736 |
Popis: | 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. Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Borelli, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Madrid, Viviana Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Raschia, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Rebolledo, Oscar R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina |
Databáze: | OpenAIRE |
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