Glucose sensing mechanisms in hypothalamic cell models: glucose inhibition of AgRP synthesis and secretion.

摘要: Glucose-sensing neurons play a role in energy homeostasis, yet how orexigenic sense glucose remains unclear. As models of glucose-inhibited (GI) neurons, mHypoE-29/1 and mHypoA-NPY/GFP cells express the essential neuropeptide AgRP sensing machinery. Exposure to increasing concentrations or analog 2-deoxyglucose (2-DG) results decrease mRNA levels. Taste receptor, Tas1R2 expression was reduced by glucose, whereas 2-DG Tas1R3 Increasing elicited rise Akt neuronal nitric oxide synthase (nNOS) phosphorylation, CaMKKβ levels, reduction AMP-kinase alpha phosphorylation. Inhibitors NOS cystic fibrosis transmembrane conductance regulator (CFTR) prevented secretion with suggesting pivotal for nNOS CFTR glucose-sensing. These possess hallmark characteristics GI can be used disentangle mechanisms which glucose.