Sitagliptin prevents the development of metabolic and hormonal disturbances, increased â-cell apoptosis and liver steatosis induced by a fructose-rich diet in normal rats

MAIZTEGUI B; BORELLI MI; MADRID V; DEL ZOTTO H; RASCHIA A; FRANCINI F; MASSA ML; FLORES L; REBOLLEDO O; GAGLIARDINO JJ

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: London; Año: 2011 p. 73 - 80

0143-5221

ABSTRACT The aim of this study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, â-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% 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/rat) or exendin-4 (CE and FE; 0.35 nmol/kg body wt, ip). Water and food intake, oral glucose tolerance, plasma glucose, triglyceride, insulin and fructosamine concentration, HOMA-IR, HOMA-â and liver triglyceride content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose tolerance), plasma triglyceride, fructosamine and insulin levels, HOMA-IR and HOMA-â indexes, and liver triglyceride content were significantly higher in F rats. Islet â-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 â-cell mass and fatty liver. Thus, these compounds ? useful to treat type 2 diabetes ? would also prevent/delay the progression of early metabolic and tissue markers of this disease.