Sitagliptin and exendin-4 effect upon impaired metabolism and decreased â-cell mass

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

Buenos Aires

Congreso; The 1st Latin America Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy); 2010

Academy for Clinical Debates and Controversies in medicine

Background: Fructose (F) administration to normal rats increases insulin resistance (IR), serum triglyceride (T), fructosamine and insulin (I) levels and impairs glucose (G) tolerance. Aim: to study the effect of exendin-4 (E) and sitagliptin (S) on the mentioned abnormalities and â-cell mass. Methodology: Normal male Wistar rats received for 3 weeks a commercial diet and water without (control, C) or with 10% F. C and F rats received E (0.70 nmol/kg/day; CE and FE) or S (115 mg/rat/day; CS and FS). We measured G, T, fructosamine and I and performed an oral G tolerance test. We also performed a pancreas morphometric analysis and measured liver T content. Results: blood G levels: no differences among groups; T (mg/dl): Fvs.C, 101.7±10.8 vs. 42.4±0.7; FE, 64.7±7.7 and FS, 60.2±4.5; I(ng/ml): Fvs.C, 0.98±0.19 vs. 0.33±0.01; FE, 0.7±0.17 and FS, 0.35±0.09; fructosamine (µMol/L): Fvs.C, 218.6±8.2 vs. 175.1±8.5; FE, 154.6±8.1 and FS, 172.5±6.8 and liver T content (µg/100 mg tissue): Fvs.C, 476.4±29.9 vs. 374.7±29.9); FE, 374.7±29.9 and FS, 299.8±. HOMA-IR was higher in F (4.9±0.1 vs. 2.0±0.4, p<0.05) becoming close to C values after E and S treatment. The area under the G curve was significantly higher in F, returning to near C levels in FE and FS. â-cell mass: Fvs.C, 3.2±0.4 vs. 5-0±0.45,p<0.05; FE, 9.54±1.8 and FS, 5.32±0.7; â-cell apoptosis rate: Fvs.C, 0.48±0.02 vs. 0.18±0.02; FE, 0.14±0.03 and FS, 0.18±0.02. E and S increased â-cell mass and decreased â-cell apoptosis Conclusion: incretins reverse F-induced metabolic abnormalities and prevents â-cell decrease by lowering their apoptosis.