CONICET | Buscador de Institutos y Recursos Humanos

Background and aims: To study the effects of insulin resistance (IR) induced by dietary manipulation upon islet PMCA activity and expression, insulin secretion and glucose metabolism. Material and Methods: ormal male Wistar rats were fed a commercial diet and water without (control) or with 10% fructose (FRD). After 21 days the animals were sacrificed to measure plasma glucose, triglyceride and insulin levels, and to remove the pancreas for immunocytochemical studies and isolate islets to measure insulin release, glucose metabolism, PMCA activity and transcription/expression of PMCA isoforms. Results: Body weight and plasma glucose levels were similar in both groups, but FRD rats have significantly higher levels of triglyceride and insulin, insulin:glucose ratio and HOMA-R index. FRD islets released more insulin in response to glucose and metabolized more glucose than control islets. FRD islets showed a significant decrease in protein content of PMCA2, an increase of PMCA3, and no significant changes in PMCAs 1 and 4. PMCA activity was significantly lower in these islets, but this difference disappeared when calmodulin activity was blocked with calmidazolium. Beta-cell mass decreased significantly in FRD rats, with no significant differences in the pancreatic PMCA cellular distribution pattern. Conclusions: FRD simultaneously induced IR, a decrease in ¦Â-cell mass, a decrease in PMCA activity, and an increase in glucose metabolism of the islets. Functional changes favor the compensatory greater release of insulin necessary to cope with the IR state, maintaining glucose homeostasis within normal range. Changes in PMCA activity and isoform expression play a modulatory role upon insulin secretion during long-term adaptation to an increased hormone demand.