Linked Life Data

12086933

Source:http://linkedlifedata.com/resource/pubmed/id/12086933

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pubmed-article:12086933pubmed:abstractTextSpecialized neurons utilize glucose as a signaling molecule to alter their firing rate. Glucose-excited (GE) neurons increase and glucose-inhibited (GI) neurons reduce activity as ambient glucose levels rise. Glucose-induced changes in the ATP-to-ADP ratio in GE neurons modulate the activity of the ATP-sensitive K(+) channel, which determines the rate of cell firing. The GI glucosensing mechanism is unknown. We postulated that glucokinase (GK), a high-Michaelis constant (K(m)) hexokinase expressed in brain areas containing populations of GE and GI neurons, is the controlling step in glucosensing. Double-label in situ hybridization demonstrated neuron-specific GK mRNA expression in locus ceruleus norepinephrine and in hypothalamic neuropeptide Y, pro-opiomelanocortin, and gamma-aminobutyric acid neurons, but it did not demonstrate this expression in orexin neurons. GK mRNA was also found in the area postrema/nucleus tractus solitarius region by RT-PCR. Intracarotid glucose infusions stimulated c-fos expression in the same areas that expressed GK. At 2.5 mmol/l glucose, fura-2 Ca(2+) imaging of dissociated ventromedial hypothalamic nucleus neurons demonstrated GE neurons whose intracellular Ca(2+) oscillations were inhibited and GI neurons whose Ca(2+) oscillations were stimulated by four selective GK inhibitors. Finally, GK expression was increased in rats with impaired central glucosensing (posthypoglycemia and diet-induced obesity) but was unaffected by a 48-h fast. These data suggest a critical role for GK as a regulator of glucosensing in both GE and GI neurons in the brain.lld:pubmed
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pubmed-article:12086933pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:12086933pubmed:articleTitleGlucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons.lld:pubmed
pubmed-article:12086933pubmed:affiliationNeurology Service, Department of Veterans Affairs Medical Center, 385 Tremont Avenue, East Orange, NJ 07018-1095, USA.lld:pubmed
pubmed-article:12086933pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12086933pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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