RESUMEN
Endurance exercise is known to enhance peripheral insulin sensitivity and reduce insulin secretion. However, it is unknown whether the latter effect is due to the reduction in plasma substrate availability or alterations in ß-cell secretory machinery. Here, we tested the hypothesis that endurance exercise reduces insulin secretion by altering the intracellular energy-sensitive AMP-activated kinase (AMPK) signaling pathway. Male Wistar rats were submitted to endurance protocol training one, three, or five times per week, over 8 weeks. After that, pancreatic islets were isolated, and glucose-induced insulin secretion (GIIS), glucose transporter 2 (GLUT2) protein content, total and phosphorylated calmodulin kinase kinase (CaMKII), and AMPK levels as well as peroxisome proliferator-activated receptor-γ coactivator-1-α (PGC-1α) and uncoupling protein 2 (UCP2) content were measured. After 8 weeks, chronic endurance exercise reduced GIIS in a dose-response manner proportionally to weekly exercise frequency. Contrariwise, increases in GLUT2 protein content, CaMKII and AMPK phosphorylation levels were observed. These alterations were accompanied by an increase in UCP2 content, probably mediated by an enhancement in PGC-1α protein expression. In conclusion, chronic endurance exercise induces adaptations in ß-cells leading to a reduction in GIIS, probably by activating the AMPK signaling pathway.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Insulina/metabolismo , Canales Iónicos/metabolismo , Islotes Pancreáticos/metabolismo , Proteínas Mitocondriales/metabolismo , Condicionamiento Físico Animal , Resistencia Física , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Transportador de Glucosa de Tipo 2/metabolismo , Secreción de Insulina , Masculino , Músculo Esquelético/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Proteínas de Unión al ARN/metabolismo , Ratas , Ratas Wistar , Factores de Transcripción/metabolismo , Proteína Desacopladora 2RESUMEN
Protein tyrosine phosphatase (PTP1B) has been implicated in the negative regulation of insulin and leptin signaling. PTP1B knockout mice are hypersensitive to insulin and leptin and resistant to obesity when fed a high-fat diet. We investigated the role of hypothalamic PTP1B in the regulation of food intake, insulin and leptin actions and signaling in rats through selective decreases in PTP1B expression in discrete hypothalamic nuclei. We generated a selective, transient reduction in PTP1B by infusion of an antisense oligonucleotide designed to blunt the expression of PTP1B in rat hypothalamic areas surrounding the third ventricle in control and obese rats. The selective decrease in hypothalamic PTP1B resulted in decreased food intake, reduced body weight, reduced adiposity after high-fat feeding, improved leptin and insulin action and signaling in hypothalamus, and may also have a role in the improvement in glucose metabolism in diabetes-induced obese rats.