Feedback Inhibition of CREB Signaling Promotes Beta Cell Dysfunction in Insulin Resistance.

ABSTRACT: Although persistent elevations in circulating glucose concentrations promote compensatory increases in pancreatic islet mass, unremitting insulin resistance causes a deterioration in beta cell function that disrupts glucose balance and signals the progression to diabetes 1. Glucagon like Peptide 1 (GLP1) agonists improve glucose tolerance in insulin resistance, although some individuals are unresponsive to treatment. Here we show that increases in GLP1 during feeding promote beta cell function in part through the PKA-mediated activation of CREB and its coactivator CRTC2 2. Mice with a knockout of CRTC2 in beta cells have impaired oral glucose tolerance due to decreases in circulating insulin concentrations. CRTC2 was found to promote beta cell function in part by stimulating the expressio

ORGANISM(S): Rattus norvegicus

SUBMITTER: Sam Van de Velde 

PROVIDER: E-GEOD-60158 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress