下丘脑细胞模型中的葡萄糖感应机制：葡萄糖对 AgRP 合成和分泌的抑制作用。
Glucose sensing mechanisms in hypothalamic cell models: glucose inhibition of AgRP synthesis and secretion.
机构信息
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5S 1A8, Canada.
出版信息
Mol Cell Endocrinol. 2014 Jan 25;382(1):262-270. doi: 10.1016/j.mce.2013.10.013. Epub 2013 Oct 18.
Glucose-sensing neurons play a role in energy homeostasis, yet how orexigenic neurons sense glucose remains unclear. As models of glucose-inhibited (GI) neurons, mHypoE-29/1 and mHypoA-NPY/GFP cells express the essential orexigenic neuropeptide AgRP and glucose sensing machinery. Exposure to increasing concentrations of glucose or the glucose analog 2-deoxyglucose (2-DG) results in a decrease in AgRP mRNA levels. Taste receptor, Tas1R2 mRNA expression was reduced by glucose, whereas 2-DG reduced Tas1R3 mRNA levels. Increasing glucose concentrations elicited a rise in Akt and neuronal nitric oxide synthase (nNOS) phosphorylation, CaMKKβ levels, and a reduction of AMP-kinase alpha phosphorylation. Inhibitors of NOS and the cystic fibrosis transmembrane conductance regulator (CFTR) prevented a decrease in AgRP secretion with glucose, suggesting a pivotal role for nNOS and the CFTR in glucose-sensing. These models possess the hallmark characteristics of GI neurons, and can be used to disentangle the mechanisms by which orexigenic neurons sense glucose.
葡萄糖感应神经元在能量平衡中发挥作用，但食欲神经元如何感应葡萄糖仍不清楚。作为葡萄糖抑制（GI）神经元的模型，mHypoE-29/1 和 mHypoA-NPY/GFP 细胞表达必需的食欲肽 AgRP 和葡萄糖感应机制。暴露于葡萄糖或葡萄糖类似物 2-脱氧葡萄糖（2-DG）的浓度增加会导致 AgRP mRNA 水平降低。葡萄糖降低了味觉受体 Tas1R2 mRNA 的表达，而 2-DG 降低了 Tas1R3 mRNA 水平。增加葡萄糖浓度会引起 Akt 和神经元型一氧化氮合酶（nNOS）磷酸化、钙调蛋白激酶 β（CaMKKβ）水平升高以及 AMP 激酶 α 磷酸化减少。NOS 和囊性纤维化跨膜电导调节剂（CFTR）的抑制剂可防止葡萄糖引起 AgRP 分泌减少，表明 nNOS 和 CFTR 在葡萄糖感应中起关键作用。这些模型具有 GI 神经元的标志性特征，可用于阐明食欲神经元感应葡萄糖的机制。
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