期刊
CLINICAL SCIENCE
卷 120, 期 1-2, 页码 73-80出版社
PORTLAND PRESS LTD
DOI: 10.1042/CS20100372
关键词
beta-cell mass; exendin-4; hypertriglyceridaemia; insulin resistance; pre-diabetes; sitagliptin
资金
- Merck, Sharp & Dohme, Argentina
- National Research Council [R1550/07]
The aim of the present study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, beta-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-beta (HOMA for beta-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-beta indexes, and liver triacylglycerol content were significantly higher in F rats. Islet beta-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 beta-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.
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