CENEXA   05419
CENTRO DE ENDOCRINOLOGIA EXPERIMENTAL Y APLICADA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of Sitagliptin and Exendin-4 on Metabolic Homeostasis in Rats with Dietary-Induced Insulin Resistance
Autor/es:
MASSA L; FRANCINI F; MAIZTEGUI B; MADRID V; RASCHIA A; FLORES L; DEL ZOTTO H; BORELLI MI; GAGLIARDINO JJ
Lugar:
New Orleans, Estados Unidos
Reunión:
Congreso; 69th Scientific Sessions American Diabetes Association.; 2009
Institución organizadora:
American Diabetes Association
Resumen:
We studied the effect of sitagliptin (S) and exendin-4 (E) on fructose-induced increase of serum triglyceride and insulin levels, insulin resistance (IR) and liver enzymes, and impairment of glucose tolerance. Normal male Wistar rats received a standard commercial diet and water without (control, C) or with 10% F for 3 weeks. Simultaneously, C and F received E (0.35 nmol/kg/day; CE and FE) or S (115mg/rat/day; CS and FS). Fifteen h fasted animals were bled at 0, 30 and 120 min after an oral glucose (1g/kg) load to measure glucose, triglyceride and insulin concentrations, and HOMA-R. Animals were sacrificed removing the liver to determine glucokinase (GK) and glucose-6-phosphate dehydrogenase (G6PDH) activity. No significant differences in food consumption were recorded among groups. Body weight of F rats increased significantly as compared to C but it was significantly lower in FE and FS. Comparable blood glucose levels were measured in all groups, but F had significantly higher triglyceride and insulin levels, which decreased to almost control values in FE and FS. HOMA-R was significantly higher in F (4.9± vs. 2.0±0.4) becoming close to C values after E and S treatment. The glucose area under the curve (AUC) was significantly higher in F, returning to near control levels in FE (2480±401) and FS (3183±230). FS had higher hepatic GK (6.8±0.2 vs 3.8±0.3 mU/mg protein, p<0.001) and G6PDH (0.17±0.01 vs 0.06±0.01 mU/mg protein, p<0.001) activity. These high values returned almost to control levels in FE and FS rats.
F-induced changes
Glucose (mg/dl)
Triglyceride (mg/dl)
Insulin (ng/ml)
HOMA-R
OGT (AUC)
C
80.8±2.3
42.4±0.7
0.33±0.08
2.00±0.4
3660±395
CE
75.3±1.7
42.5±5.8
0.25±0.06
1.18±0.2
2915±499
CS
80.1±2.9
56.2±8.8
0.31±0.06
1.39±0.3
3034±627
F
89±4
101.7±10.8*
0.98±0.19*
4.97±1.2*
5595±259
FE
75.5±3.2
64.7±7.7*
0.7±0.17
3.52±1.0
2480±401
FS
84.3±4.8
60.2±4.5*
0.35±0.09*
1.58±0.4*
3183±230
Results are means±SEM; n= 20 rats each group.*P< 0.05 compared with its corresponding control.
Our results show a new therapeutic profile of E and S effects: they decrease IR and improve lipid and glucose metabolism as well as liver enzyme levels