CENEXA   05419
CENTRO DE ENDOCRINOLOGIA EXPERIMENTAL Y APLICADA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effects of fructose-rich diet-induced insulin resistance on PMCA isoform transcription, expression and activity in rat pancreatic islet and its relationship with insulin secretion.
Autor/es:
ALZUGARAY ME; GARCÍA ME; ROSSI JPFC; GAGLIARDINO JJ
Lugar:
Helsingor, Dinamarca
Reunión:
Workshop; EASD Islet Study Group Symposium 2006. Beta cell replacement/regeneration in diabetes therapy; 2006
Institución organizadora:
European Association for the Study of Diabetes
Resumen:
Aim: To study the effect of fructose-rich diet (FRD)-induced insulin resistance on rat islet PMCA activity, transcription and expression. Material and Methods: Normal male rats received a commercial diet with tap water (control) or a 10% fructose solution (FRD) for 21 days. After this period we sacrificed the animals measuring plasma glucose, triglyceride and insulin levels and removed the whole pancreases. We isolated islets to measure glucose-induced insulin secretion and PMCA transcription (RT-PCR), expression (Western blot) and activity. Results: We recorded similar body weight and normal plasma glucose levels in both groups, but FRD animals had significantly higher triglyceride (158.9 ± 5.5 vs.98.5 ± 3.5 mg/dl; p< 0.0001) and insulin (1.16 ± 0.07 vs. 0.77 ± 0.05 ng/ml; p<0.02) levels and Homa index values (22.1 ± 3.2 vs. 9.7 ± 1.42; p <0.001). FRD islets released more insulin in response to 8-20  mM glucose (p <0.02), but not at lower glucose concentrations. FRD islets showed a significant increase in PMCA2 transcription (p< 0.05) together with a decrease in PMCA2 expression (p <0.001) and an increase in PMCA3 (p <0.01), with no changes in PMCA 1 and 4. PMCA activity was lower in FRD (1.22 ± 0.09 vs.1.57 ± 0.11 pmoles Pi/h/µg prot; p<0.02), but this difference disappeared in the presence of calmidazolium (calmodulin inhibitor). Conclusion: FRD-induced insulin resistance promotes a decrease in islet PMCA activity, probably due to a decrease in PMCA2 expression and a consequent increase in glucose- induced insulin secretion.