Abstract
Results Using insulin and glucagon secretion protocols with fresh islets isolated from C57BL6 mice, we observed that CORT reduced the glucose-stimulated insulin secretion (GSIS) in a similar magnitude from that of SST (p<0.01), an effect mediated by SST-R5 receptor. Glucagon secretion in response to 0.5 mM glucose was completely abrogated in the presence of CORT (p<0.001), as well as for SST. Beta cell function were further investigated and we observed that the reduction in insulin secretion was paralleled by a decrease in the glucose-induced calcium levels observed by fura-2 calcium imaging (p<0.001). As opposed to the effects on SST, the effect of CORT in beta cell calcium load was blocked by specific SST-R5 receptor antagonist, suggesting a higher affinity of CORT for this receptor. In addition, CORT reduced beta cell membrane potential and abolished action potential firings in perforated patch clamp experiments (p<0.001). CORT also diminished calcium currents in whole cell patch clamp experiments.
Highlights
Cortistatin-14 (CORT) is a neuropeptide commonly expressed in inhibitory neurons of the central nervous system (CNS) with structural, pharmacological and functional similarity to somatostatin (SST)
Using insulin and glucagon secretion protocols with fresh islets isolated from C57BL6 mice, we observed that CORT reduced the glucose-stimulated insulin secretion (GSIS) in a similar magnitude from that of SST (p
Glucagon secretion in response to 0.5 mM glucose was completely abrogated in the presence of CORT (p
Summary
Cortistatin-14 (CORT) is a neuropeptide commonly expressed in inhibitory neurons of the central nervous system (CNS) with structural, pharmacological and functional similarity to somatostatin (SST). Cortistatin hyperpolarizes pancreatic beta cell membrane and reduces glucose-stimulated insulin secretion Alex Rafacho*, Manuel Castellano-Muñoz, Paloma Alonso-Magdalena, Esperanza Irles, Melisa Bello, Jean Vetorazzi, Beatriz Merino, Sergi Soriano, Pau Iborra, Antonia Ruiz, Raúl M Luque, Angel Nadal, Ivan Quesada From 20th Brazilian Diabetes Society Congress Porto Alegre, Brazil.
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