Fasting enhances the response of arcuate neuropeptide Y-glucose-inhibited neurons to decreased extracellular glucose

作者：Murphy Beth Ann; Fioramonti Xavier; Jochnowitz Nina; Fakira Kurt; Gagen Karen; Contie Sylvain; Lorsignol Anne; Penicaud Luc; Martin William J; Routh Vanessa H^*

来源：American Journal of Physiology - Cell Physiology, 2009, 296(4): C746-C756.

DOI：10.1152/ajpcell.00641.2008

• arcuate nucleus
• glucose-inhibited neuron
• adenosine 5 '-monophosphate kinase
• leptin
• fasting

Murphy BA, Fioramonti X, Jochnowitz N, Fakira K, Gagen K, Contie S, Lorsignol A, Penicaud L, Martin WJ, Routh VH. Fasting enhances the response of arcuate neuropeptide Y-glucose-inhibited neurons to decreased extracellular glucose. Am J Physiol Cell Physiol 296: C746-C756, 2009. First published February 11, 2009; doi:10.1152/ajpcell.00641.2008.-Fasting increases neuropeptide Y (NPY) expression, peptide levels, and the excitability of NPY-expressing neurons in the hypothalamic arcuate (ARC) nucleus. A subpopulation of ARC-NPY neurons (similar to 40%) are glucose-inhibited (GI)-type glucose-sensing neurons. Hence, they depolarize in response to decreased glucose. Because fasting enhances NPY neurotransmission, we propose that during fasting, GI neurons depolarize in response to smaller decreases in glucose. This increased excitation in response to glucose decreases would increase NPY-GI neuronal excitability and enhance NPY n. Using an in vitro hypothalamic explant system, we show that fasting enhances NPY release in response to decreased glucose concentration. By measuring relative changes in membrane potential using a membrane potential-sensitive dye, we demonstrate that during fasting, a smaller decrease in glucose depolarizes NPY-GI neurons. Furthermore, incubation in low (0.7 mM) glucose enhanced while leptin (10 nM) blocked depolarization of GI neurons in response to decreased glucose. Fasting, leptin, and glucose-induced changes in NPY-GI neuron glucose sensing were mediated by 5'-AMP-activated protein kinase (AMPK). We conclude that during energy sufficiency, leptin reduces the ability of NPY-GI neurons to sense decreased glucose. However, after a fast, decreased leptin and glucose activate AMPK in NPY-GI neurons. As a result, NPY-GI neurons become depolarized in response to smaller glucose fluctuations. Increased excitation of NPY-GI neurons enhances NPY release. NPY, in turn, shifts energy homeostasis toward increased food intake and decreased energy expenditure to restore energy balance.

• 出版日期2009-4