RESUMEN
The renin-angiotensin system modulates insulin action. Angiotensin type 1 receptor exerts a deleterious effects while the angiotensin type 2 receptor (AT2R) appears to have beneficial effects providing protection against insulin resistance and type 2 diabetes. Although recent reports indicate that agonism of AT2R ameliorates diabetes and insulin resistance, the phenotype of AT2R-knockout mice seems to be controversial relating this aspect. Thus, in this study we have explored the role of AT2R in the control of insulin action. To that end, C57Bl/6 mice were administered the synthetic AT2R antagonist PD123319 for 21days (10mg/kg/day ip); vehicle treated animals were used as control. Glucose tolerance, metabolic parameters, in vivo insulin signaling in main insulin-target tissues as well as levels of adiponectin, TNF-α, MCP-1 and IL-6 in adipose tissue were assessed. AT2R blockade with PD123319 induced a marginal effect on glucose homeostasis but an important reduction in the insulin-induced phosphorylation of the insulin receptor and Akt in both liver and adipose tissue. Insulin signaling in skeletal muscle remained unaltered after treatment with PD123319, which could explain the minimal effect on glucose homeostasis induced by PD123319. Our current results reinforce the notion that the AT2R has a physiological role in the conservation of insulin action.
Asunto(s)
Bloqueadores del Receptor Tipo 2 de Angiotensina II/administración & dosificación , Diabetes Mellitus Tipo 2/genética , Hipertensión/genética , Receptor de Angiotensina Tipo 2/genética , Adiponectina/genética , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Angiotensina II/metabolismo , Animales , Quimiocina CCL2/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/patología , Imidazoles/administración & dosificación , Insulina/genética , Insulina/metabolismo , Resistencia a la Insulina/genética , Interleucina-6/genética , Losartán/administración & dosificación , Ratones , Ratones Noqueados , Piridinas/administración & dosificación , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Phaseolus vulgaris (common bean) is an agronomic important legume crop native to America, where two centres of genetic diversification (GD) are recognised, one in Mesoamerica and the other in the south Andes. Mesoamerican bean accessions have preferential and more efficient nodulation with Rhizobium etli strains carrying the allele nodC type-α, which is predominant in soils of Mesoamerica. It was previously demonstrated that the host nuclear factor NF-YC1, which is involved in nodule formation and rhizobial infection, contributes to this preferential selection and enhances nodulation in the domesticated accession NAG12 from Mesoamerica. Here, we show that both domesticated and wild Mesoamerican beans exhibit higher nodulation performance with a nodC type-α than with a nodC type-δ strain. Transcripts of NF-YC1 significantly increased in roots of these accessions 24 h post-inoculation (hpi) with the nodC type-α strain. On the other hand, accessions from the Andean GD centre formed a higher number of nodules with a strain carrying the nodC type-δ, which is predominant in Andean soils. However, NF-YC1 transcript levels did not exhibit significant changes in Andean accessions upon inoculation with the nodC type-δ strain, at least at 24 hpi. RNA interference (RNAi)-mediated gene silencing of NF-YC1 in the domesticated Andean accession Alubia showed that NF-YC1 or a closely related member of this family is required for nodule formation and bacterial infection, in agreement with observations in Mesoamerican common beans. Isolation and sequencing of the full-length ORF of NF-YC1 from Alubia revealed that it was identical to the sequence previously identified in the Mesoamerican accession NAG12. Interestingly, overexpression of NF-YC1 had a negative impact on nodule formation in the Alubia accession, independently of the R. etli lineage. Our findings suggest that transcriptional and functional variation of NF-YC1 occurs among genetically diverse bean accessions, which might positively or negatively contribute to the fine-tuning mechanisms that regulate nodule formation in the common bean-R. etli symbiosis.