Objetivo Normal gestation is associated with substantial changes in maternal metabolism including a marked increase in insulin resistance and mild cholestasis, hypercholesterolaemia, and hypertriglyceridemia at later gestational weeks. In some predisposed women, the metabolic changes are adequately severe to lead to development of gestational disorders of pregnancy including gestational diabetes mellitus (GDM) and intrahepatic cholestasis of pregnancy (ICP). Indeed, women with ICP are more susceptible to developing GDM and have significant biochemical and endocrine changes such as increased basal endogenous glucose production, decreased insulin sensitivity, and reduced GLP1 secretion from enteroendocrine L-cells that result in altered carbohydrate metabolism while they are cholestatic. The applicant hypothesises that reproductive hormones and their metabolites play an integral role in beta-cell adaptation in pregnancy through altered nuclear farnesoid-X-receptor (FXR) and G-protein coupled receptor TGR5 activity in the enteroendocrine L-cells and pancreatic islets. The applicant hypothesises that reproductive hormones and their metabolites play an integral role in beta-cell adaptation in pregnancy through altered nuclear farnesoid-X-receptor (FXR) and G-protein coupled receptor TGR5 activity in the enteroendocrine L-cells and pancreatic islets. There are emerging data to show that the bile acid receptors FXR and TGR5 play a pivotal role in glucose homeostasis and susceptibility to diabetes mellitus, but their role in altered glucose metabolism in pregnancy is poorly understood. The aberrant BA homeostasis during ICP may further contribute to the aetiology of GDM, by affecting FXR and TGR5 signalling in the in the gut and endocrine pancreas. It is also likely that that BA toxicity in ICP can increase beta-cell apoptosis, thereby interfering with their ability to adapt in pregnancy and thus compromising the demand for insulin to maintain maternal glucose homeostasis. Ámbito científico medical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesclinical medicineobstetricsnatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydratesmedical and health sciencesbasic medicinephysiologyhomeostasis Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Convocatoria de propuestas FP7-PEOPLE-2013-IEF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IEF - Intra-European Fellowships (IEF) Coordinador KING'S COLLEGE LONDON Aportación de la UE € 221 606,40 Dirección Strand WC2R 2LS London Reino Unido Ver en el mapa Región London Inner London — West Westminster Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Paul Labbett (Mr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos