Title: Fasting Enhances the Response of Arcuate Neuropeptide Y (npy)-glucose-inhibited Abbreviated Title: Fasting Modulates Glucose Responses in Npy Neurons
نویسندگان
چکیده
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 (~ 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 neurotransmission. 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 activates 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 towards increased food intake and decreased energy expenditure in order to restore energy balance.
منابع مشابه
Fasting enhances the response of arcuate neuropeptide Y-glucose-inhibited neurons to decreased extracellular glucose.
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 ( approximately 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...
متن کاملNeuropeptide Y cells represent a distinct glucose-sensing population in the lateral hypothalamus.
The maintenance of appropriate glucose levels is necessary for survival. Within the brain, specialized neurons detect glucose fluctuations and alter their electrical activity. These glucose-sensing cells include hypothalamic arcuate nucleus neurons expressing neuropeptide Y (NPY) and lateral hypothalamic area (LHA) neurons expressing orexin/hypocretins (ORX) or melanin-concentrating hormone (MC...
متن کاملArcuate Na+,K+-ATPase senses systemic energy states and regulates feeding behavior through glucose-inhibited neurons.
Feeding is regulated by perception in the hypothalamus, particularly the first-order arcuate nucleus (ARC) neurons, of the body's energy state. However, the cellular device for converting energy states to the activity of critical neurons in ARC is less defined. We here show that Na(+),K(+)-ATPase (NKA) in ARC senses energy states to regulate feeding. Fasting-induced systemic ghrelin rise and gl...
متن کاملDifferential effects of central leptin, insulin, or glucose administration during fasting on the hypothalamic-pituitary-thyroid axis and feeding-related neurons in the arcuate nucleus.
The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons of the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) and alpha-MSH/cocaine and amphetamine-regulated transcript. Because the central administration of leptin is capable of preventing the inhibitory effects of fastin...
متن کاملAttenuation of diabetic hyperphagia in neuropeptide Y--deficient mice.
The combined effects of increased hypothalamic signaling by neuropeptide Y (NPY) and decreased signaling by melanocortins are hypothesized to stimulate food intake when body fat stores are depleted. To investigate NPY's role in the hyperphagic response to uncontrolled diabetes, streptozotocin (STZ) (200 mg/kg intraperitoneally) or saline vehicle was given to NPY-deficient (Npy(--/--)) and wild-...
متن کامل