Skip to main content
SpringerLink
Log in

Glucose Sensing Neurons

  • Reference work entry
  • First Online:
Book cover Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

It is clear that the brain plays a key role in the maintenance of glucose homeostasis. The exact mechanism(s) by which this occurs remains a mystery. However, glucose sensing neurons stand out as prime candidates which enable the brain to sense and respond to changing glucose levels. These neurons are located in key brain regions involved in the regulation of glucose and energy homeostasis. They are also located in the periphery. Glucose sensing neurons are exquisitely sensitive to small changes in extracellular glucose within the physiological range. Their glucose sensitivity becomes impaired under conditions where central glucose sensing mechanisms become dysfunctional. This review discusses the locations of central and peripheral glucose sensing neurons and the mechanisms by which they sense glucose. Putative physiological roles of both central and peripheral glucose sensors are described. Finally, the relationship between glucose and other nutrient signals to the brain is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 249.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

Ach:

acetylcholine

AMPK:

AMP activated protein kinase

ARC:

arcuate nucleus of the hypothalamus

CRR:

counterregulatory response to hypoglycemia

CSF:

cerebrospinal fluid

GABA:

γ-aminobutyric acid

GE neurons:

glucose-excited neurons

GI neurons:

glucose-inhibited neurons

GK:

glucokinase

GLUT:

glucose transporter

HGE:

high glucose excited

HGI:

high glucose inhibited

HK:

hexokinase

KATP channel:

ATP-sensitive K+channel

LDH:

lactate dehydrogenase

LTD:

long term potentiation

MCT:

Monocarboxylate transporter

αMSH:

alpha melanocyte stimulating hormone

nNOS:

neuronal nitric oxide synthase

NO:

nitric oxide

NPY:

neuropeptide Y

NTS:

nucleus of the solitary tract

OA:

oleic acid

PED:

presynaptically excited by decreased glucose

PER:

presynaptically excited by raised glucose

PIR:

presynaptically inhibited by raised glucose

POMC:

proopiomelanocortin

PVN:

paraventricular nucleus of the hypothalamus

5TG:

5 thioglucose

T2DM:

type 2 diabetes mellitus

VSAC:

volume sensitive anion channel

VMH:

Ventromedial hypothalamus

VMN:

ventromedial hypothalamic nucleus

References

  • Ad L. 1981. Raphe pallidus and raphe obscurus projections to the intermediolateral cell column in the rat. Brain Res 222: 129–133.

    Article  Google Scholar 

  • Almeida A, Bolanos JP. 2001. A transient inhibition of mitochondrial ATP synthesis by nitric oxide synthase activation triggered apoptosis in primary cortical neurons. J Neurochem 77: 676–690.

    Article  CAS  PubMed  Google Scholar 

  • Almeida A, Cidad P, Bolanos JP. 2002. Nitric oxide accounts for an increased glycolytic rate in activated astrocytes through a glycogenolysis-independent mechanism. Brain Res 945: 131–134.

    Article  CAS  PubMed  Google Scholar 

  • Almeida A, Moncada S, Bolanos JP. 2003. Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat Cell Biol 6: 45–52.

    Article  PubMed  CAS  Google Scholar 

  • Almeida A, Moncada S, Bolanos JP. 2004. Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat Cell Biol 6: 45–51.

    Article  CAS  PubMed  Google Scholar 

  • Almeida A, Almeida J, Bolanos JP, Moncada S. 2001. Different responses of astrocytes and neurons to nitric oxide: The role of glycolytically generated ATP in astrocyte protection. Proc Natl Acad Sci 98: 15294–15299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almeida A, Cidad P, Delgado-Esteban M, Fernandez E, Garcia-Nogales P, et al. 2005. Inhibition of mitochondrial respiration by nitric oxide: Its role in glucose metabolism and neuroprotection. J Neurosci Res 79: 166–171.

    Article  CAS  PubMed  Google Scholar 

  • Alnaes E, Rahamimoff R. 1975. On the role of mitochondria in transmitter release from motor nerve terminals. J Physiol 248: 285–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alvarez-Buylla R, de Alvarez-Buylla ER. 1998. Carotid sinus receptors participate in glucose homeostasis. Respir Physiol 72: 347–360.

    Article  Google Scholar 

  • Ambiel CR, Alves-Do-Prado W. 1997. Neuromuscular facilitation and blockade induced by L-arginine and nitric oxide in the rat isolated diaphragm. Gen Pharmacol 28: 789–794.

    Article  CAS  PubMed  Google Scholar 

  • Ames AI. 2000. CNS energy metabolism as related to function. Brain Res Rev 34: 42–68.

    Article  CAS  PubMed  Google Scholar 

  • Amiel SA, Archibald HR, Chusney G, Williams AJ, Gale EA. 1991. Ketone infusion lowers hormonal responses to hypoglycaemia: Evidence for acute cerebral utilization of a non-glucose fuel. Clin Sci (Lond) 81: 189–194.

    Article  CAS  Google Scholar 

  • Anand BK, China GS, Sharma KN, Dua S, Singh B. 1964. Activity of single neurons in the hypothalamus feeding centers: Effect of glucose. Am J Physiol 2207: 1146–1154.

    Article  Google Scholar 

  • Andrew S, Ritter S. 2003. Localized glucoprivation of hindbrain but not hypothalamic sites stimulates CORT and glucagon secretion. Appetite 4: 315.

    Google Scholar 

  • Ashcroft FM, Gribble FM. 1999. ATP-sensitive K+ channels and insulin secretion: Their role in health and disease. Diabetologia 42: 903–919.

    Article  CAS  PubMed  Google Scholar 

  • Ashford MLJ, Boden PR, Treherne JM. 1990a. Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. Pfugers Arch Eur J Physiol 415: 479–483.

    Article  CAS  Google Scholar 

  • Ashford MLJ, Boden PR, Treherne JM. 1990b. Tolbutamide excites rat glucoreceptive ventromedial hypothalamic neurones by indirect inhibition of ATP-sensitive K+ channels. Br J Pharmacol 101: 531–540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ashford MLJ, Sturgess NC, Trout NJ, Gardner NJ, Hales CN. 1988. Adenosine-5′-triphosphate-sensitive ion channels in neonatal rat cultured central neurons. Pfugers Arch Eur J Physiol 412: 297–304.

    Article  CAS  Google Scholar 

  • Bago M, Marson L, Dean C. 2002. Serotonergic projections to the rostroventrolateral medulla from midbrain and raphe nuclei. Brain Res 945: 249–258.

    Article  CAS  PubMed  Google Scholar 

  • Bai FL, Yamano M, Shiotani Y, Emson PC, Smith AD, et al. 1985. An arcuato-paraventricular and -dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenaline in the rat. Brain Res 331: 172–175.

    Article  CAS  PubMed  Google Scholar 

  • Balon TW, Nadler JL. 1997. Evidence that nitric oxide increases glucose transport in skeletal muscle. J Appl Physiol 82: 359–363.

    Article  CAS  PubMed  Google Scholar 

  • Bataille D, Heron L, Virsolvy A, Peyrollier K, LeCam A, et al. 1999. alpha-Endosulfine, a new entity in the control of insulin secretion. Cell Mol Life Sci 56: 78–84.

    Article  CAS  PubMed  Google Scholar 

  • Best L, McLaughlin J. 2004. Nutrients as regulators of endocrine and neuroendocrine secretion. Topics in Current Genetics. Winderickx, Taylor P, editors. Berlin: Springer-Verlag; pp. 70–111.

    Google Scholar 

  • Best L, Brown PD, Tomlinson S. 1997. Anion fluxes, volume regulation and electrical activity in the mammalian pancreatic beta-cell. Exp Physiol 82: 957–966.

    Article  CAS  PubMed  Google Scholar 

  • Bestetti G, Rossi GL. 1980. Hypothalamic lesions in rats with longterm streptozotocin-induced diabetes mellitus. A semiquantitative light and electron-microscopic study. Acta Neuropathol 52: 119–127.

    Article  CAS  PubMed  Google Scholar 

  • Bestetti G, Rossi GL. 1982. Hypothalamic changes in diabetic Chinese hamsters: A semiquantitative, light and electron microscopic study. Lab Invest 47: 516–522.

    CAS  PubMed  Google Scholar 

  • Bi S, Ladenheim EE, Schwartz GJ, Moran TH. 2001. A role for NPY overexpression in the dorsomedial hypothalamus in hyperphagia and obesity of OLETF rats. Am J Physiol 281: R254–R260.

    CAS  Google Scholar 

  • Biggers DW, Myers SR, Neal D, Stinson R, Cooper NB, et al. 1989. Role of brain in counterregulation of insulin-induced hypoglycemia in dogs. Diabetes 38: 7–16.

    Article  CAS  PubMed  Google Scholar 

  • Billington CJ, Levine AS. 1992. Hypothalamic neuropeptide Y regulation of feeding and energy metabolism. Curr Opin Neurobiol 2: 847–851.

    Article  CAS  PubMed  Google Scholar 

  • Bin-Jaliah I, Maskell PD, Kumar P. 2004. Indirect sensing of insulin-induced hypoglycaemia by the carotid body in the rat. J Physiol Online 556: 255–266.

    Article  CAS  Google Scholar 

  • Bittar PG, Charnay Y, Pellerin L, Bouras C, Magistretti PJ. 1996. Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab 16: 1079–1089.

    Article  CAS  PubMed  Google Scholar 

  • Blottner D, Luck G. 2001. Just in time and place: NOS/NO system assembly in neuromuscular junction formation. Micros Res Tech 55: 171–180.

    Article  CAS  Google Scholar 

  • Boehning D, Snyder SH. 2003. Novel neural modulators. Ann Rev Neurosci 26: 105–131.

    Article  CAS  PubMed  Google Scholar 

  • Bolanos JP, Cidad P, Garcia-Nogales P, Delgado-Esteban M, Fernandez E, et al. 2004. Regulation of glucose metabolism by nitrosative stress in neural cells. Mol Aspects Med 25(1–2): 61–73.

    Article  CAS  PubMed  Google Scholar 

  • Bolanos JP, Garcia-Nogales P, Vega-Agapito V, Delgado-Esteban M, Cidad P, et al. 2001. Nitric oxide-mediated mitochondrial impairment in neural cells: A role for glucose metabolism in neuroprotection. Prog Brain Res 132: 441–454.

    Article  CAS  PubMed  Google Scholar 

  • Borg MA, Tamborlane WV, Shulman GI, Sherwin RS. 2003. Local lactate perfusion of the ventromedial hypothalamus suppresses hypoglycemic counterregulation. Diabetes 52: 663–666.

    Article  CAS  PubMed  Google Scholar 

  • Borg WP, During MJ, Sherwin RS, Borg MA, Brines ML, et al. 1994. Ventromedial hypothalamic lesions in rats suppress counterregulatory responses to hypoglycemia. J Clin Invest 93: 1677–1682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borg WP, Sherwin RS, During MJ, Borg MA, Shulman GI. 1995. Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone release. Diabetes 44: 180–184.

    Article  CAS  PubMed  Google Scholar 

  • Boston BA, Blaydon KM, Varnerin J, Cone RD. 1997. Independent and additive effects of central POMC and leptin pathways on murine obesity. Science 278: 1641–1644.

    Article  CAS  PubMed  Google Scholar 

  • Bradley SJ, Kingwell BA, McConell GK. 1999. Nitric oxide synthase inhibition reduces leg glucose uptake but not blood flow during dynamic exercise in humans. Diabetes 48: 1815–1821.

    Article  CAS  PubMed  Google Scholar 

  • Byrum DC, Guyenet PG. 1987. Afferent and efferent connections of the A5 noradrenergic cell group in the rat. J Comp Neurol 261: 529–542.

    Article  CAS  PubMed  Google Scholar 

  • Campfield LA, Smith FJ. 1986. Functional coupling between transient declines in blood glucose and feeding behavior: Temporal relationships. Brain Res Bull 17: 427–549.

    Article  CAS  PubMed  Google Scholar 

  • Cheunsuang O, Morris R. 2005. Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors. Glia 52: 228–233.

    Article  PubMed  Google Scholar 

  • Christova T, Grozdanovic Z, Gossrau R. 1997. Nitric oxide synthase (NOS) I during postnatal development in rat and mouse skeletal muscle. Acta Histochem 99(3): 311–324.

    Google Scholar 

  • Chronwall BM, DiMaggio DA, Massari VJ, Pickel VM, Ruggiero DA, et al. 1985. The anatomy of neuropeptide-Y-containing neurons in rat brain. Neuroscience 15: 1159–1181.

    Article  CAS  PubMed  Google Scholar 

  • Cidad P, Garcia-Nogales P, Almeida A, Bolanos JP. 2001. Expression of glucose transporter GLUT3 by endotoxin in cultured rat astrocytes: The role of nitric oxide. J Neurochem 79: 17–24.

    Article  CAS  PubMed  Google Scholar 

  • Cinco DD, Potian JG, Beuve A, McArdle JJ, Routh VH. 2005. Nitric oxide integrates leptin, insulin and glucose signaling in ventromedial hypothalamic (VMH) neurons. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2005. Online. 533.8.

    Google Scholar 

  • Clement L, Cruciani-Guglielmacci C, Magnan C, Vincent M, Douared L, et al. 2002. Intracerebroventricular infusion of a triglyceride emulsion leads to both altered insulin secretion and hepatic glucose production in rats. Pflugers Arch 445: 375–380.

    Article  CAS  PubMed  Google Scholar 

  • Constantini S, Schiller Y, Cohen AM, Rahamimoff R. 1987. Pathophysiology of the neuromuscular junction in diabetic rats. Isr J Med Sci 23: 101–106.

    CAS  PubMed  Google Scholar 

  • Cruciani-Guglielmacci C, Hervalet A, Douared L, Sanders NM, Levin BE, et al. 2004. Beta oxidation in the brain is required for the effects of non-esterified fatty acids on glucose-induced insulin secretion in rats. Diabetologia 47: 2032–2038.

    Article  CAS  PubMed  Google Scholar 

  • Cryer PE. 2001. Hypoglycemia-associated autonomic failure in diabetes. Am J Physiol 281: E1115–E1121.

    CAS  Google Scholar 

  • Das UN. 2001. Is obesity an inflammatory condition? Nutrition 17: 953–966.

    Article  CAS  PubMed  Google Scholar 

  • David G. 1999. Mitochondrial clearance of cytosolic Ca(2+) in stimulated lizard motor nerve terminals proceeds without progressive elevation of mitochondrial matrix [Ca(2+)]. J Neurosci 19: 7495–7506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • David G, Barrett EF. 2000. Stimulation-evoked increases in cytosolic [Ca(2+)] in mouse motor nerve terminals are limited by mitochondrial uptake and are temperature-dependent. J Neurosci 20: 7290–7296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • David G, Barrett EF. 2003. Mitochondrial Ca2+ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals. The J Physiol 548: 425–438.

    Article  CAS  PubMed  Google Scholar 

  • David G, Barrett JN, Barrett EF. 1998. Evidence that mitochondria buffer physiological Ca2+ loads in lizard motor nerve terminals. J Physiol 509: 59–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davies SL, Roussa E, Le Rouzic P, Thevenod F, Alper SL, et al. 2004. Expression of K+-Cl- cotransporters in the [alpha]-cells of rat endocrine pancreas. Biochim Biophys Acta (BBA)-Biomembranes 1667: 7–14.

    Article  CAS  Google Scholar 

  • Del Castillo J, Katz B. 1954. Statistical factors involved in neuromuscular facilitation and depression. J Physiol 124: 574–585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Descarries LM, Cai S, Robitaille R, Josephson EM, Morest DK. 1998. Localization and characterization of nitric oxide synthase at the frog neuromuscular junction. J Neurocytol 27: 829–840.

    Article  CAS  PubMed  Google Scholar 

  • De Vries MG, Arseneau LM, Lawson ME, Beverly JL. 2003. Extracellular glucose in rat ventromedial hypothalamus during acute and recurrent hypoglycemia. Diabetes 52: 2767–2773.

    Article  CAS  PubMed  Google Scholar 

  • DiRocco RJ, Grill HJ. 1979. The forebrain is not essential for sympathoadrenal hyperglycemic response to glucoprivation. Science 204: 1112–1114.

    Article  CAS  PubMed  Google Scholar 

  • Donovan CM, Cane P, Bergman RN. 1991. Search for the hypoglycemia receptor using the local irrigation approach. Adv Exp Med Biol 291: 185–196.

    Article  CAS  PubMed  Google Scholar 

  • Donovan CM, Hamilton-Wessler M, Halter JB, Bergman RN. 1994. Primacy of liver glucosensors in the sympathetic response to progressive hypoglycemia. Proc Natl Acad Sci 91: 2863–2867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunn-Meynell AA, Routh VH, Kang L, Gaspers L, Levin BE. 2002. Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons. Diabetes 51: 2056–2065.

    Article  CAS  PubMed  Google Scholar 

  • During MJ, Leone P, Davis KE, Kerr D, Sherwin RS. 1995. Glucose modulates rat substantia nigra GABA release in vivo via ATP-sensitive potassium channels. J Clin Invest 95: 2403–2408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erdos B, Miller AM, Busija DW. 2003. Cerebrovascular dysfunction in insulin Zucker obese rats. Soc. Neurosci. Abstr. Viewer/Itinerary Planner 7.12.

    Google Scholar 

  • Etherington SJ, Everett AW. 2004. Postsynaptic production of nitric oxide implicated in long-term depression at the mature amphibian (Bufo marinus) neuromuscular junction. J Physiol 559: 507–517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans SB, Wilkinson CW, Gronbeck P, Bennett JL, Taborsky GJ Jr, et al. 2003. Inactivation of the PVN during hypoglycemia partially simulates hypoglycemia-associated autonomic failure. Am J Physiol 284: R57–R65.

    CAS  Google Scholar 

  • Evans SB, Wilkinson CW, Gronbeck P, Bennett JL, Zavosh A, et al. 2004. Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia. Am J Physiol Regul Integr Comp Physiol 286: R123–R128.

    Article  CAS  PubMed  Google Scholar 

  • Fahim MA, Al Shuaib W, Davidson N. 1999. Depolarization affects neuromuscular junction of streptozotocin-diabetic mice. Cell Mol Biol (Noisy-le-grand) 45: 259–263.

    CAS  Google Scholar 

  • Fahim MA, el-Sabban F, Davidson N. 1998. Muscle contractility decrement and correlated morphology during the pathogenesis of streptozotocin-diabetic mice. Anat Rec 251: 240–244.

    Article  CAS  PubMed  Google Scholar 

  • Fahim MA, Hasan MY, Alshuaib WB. 2000. Early morphological remodeling of neuromuscular junction in a murine model of diabetes. J Appl Physiol 89: 2235–2240.

    Article  CAS  PubMed  Google Scholar 

  • Fatt P, Katz B. 1950. Some observations on biological noise. Nature 166: 597–598.

    Article  CAS  PubMed  Google Scholar 

  • Fatt P, Katz B. 1952. Spontaneous subthreshold activity at motor nerve endings. J Physiol 117: 109–128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fioramonti X, Lorsignol A, Song Z, Routh VH, Penicaud L. 2005. Characterization of different glucose sensing neuron subpopulations in rat and mouse arcuate nucleus. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2005. Online. 812.6.

    Google Scholar 

  • Fioramonti X, Lorsignol A, Taupignon A, Penicaud L. 2004. A New ATP-Sensitive K+ Channel-Independent Mechanism Is Involved in Glucose-Excited Neurons of Mouse Arcuate Nucleus. Diabetes 53: 2767–2775.

    Article  CAS  PubMed  Google Scholar 

  • Fraley GS, Ritter S. 2003. Immunolesion of Norepinephrine and Epinephrine Afferents to Medial Hypothalamus Alters Basal and 2-Deoxy-D-Glucose-Induced Neuropeptide Y and Agouti Gene-Related Protein Messenger Ribonucleic Acid Expression in the Arcuate Nucleus. Endocrinology 144: 75–83.

    Article  CAS  PubMed  Google Scholar 

  • Fraley GS, Dinh TT, Ritter S. 2001. Immunotoxin lesion of catecholaminergic neurons innervating the medial hypothalamus elevates basal expression of and attenuates glucoprivation-induced increases in agouti gene related protein (AGRP). Abstr Soc Neurosci 31, 947.

    Google Scholar 

  • Frizzell RT, Jones EM, Davis SN, Biggers DW, Myers SR, et al. 1993. Counterregulation during hypoglycemia is directed by widespread brain regions. Diabetes 42: 1253–1261.

    Article  CAS  PubMed  Google Scholar 

  • Garcia M, Millan C, Balmaceda-Aguilera C, Castro T, Pastor P, et al. 2003. Hypothalamic ependymal-glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing. J Neurochem 86: 709–724.

    Article  PubMed  CAS  Google Scholar 

  • Garcia O, Almeida A, Massieu L, Bolanos JP. 2005. Increased mitochondrial respiration maintains the mitochondrial membrane potential and promotes survival of cerebellar neurons in an endogenous model of glutamate receptor activation. J Neurochem 92: 183–190.

    Article  CAS  PubMed  Google Scholar 

  • Gegg ME, Beltran B, Salas-Pino S, Bolanos JP, Clark JB, et al. 2003. Differential effect of nitric oxide on glutathione metabolism and mitochondrial function in astrocytes and neurones: Implications for neuroprotection/neurodegeneration? J Neurochem 86: 228–237.

    Article  CAS  PubMed  Google Scholar 

  • Geppert M, Goda Y, Hammer RE, Li C, Rosahl TW, et al. 1994. Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse. Cell 79: 717–727.

    Article  CAS  PubMed  Google Scholar 

  • Godfrey EW, Schwarte RC. 2003. The role of nitric oxide signaling in the formation of the neuromuscular junction. J Neurocytol 32: 591–602.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein BJ, Mahadev K, Wu X. 2005. Redox paradox: Insulin action is facilitated by insulin-stimulated reactive oxygen species with multiple potential signaling targets. Diabetes 54: 311–321.

    Article  CAS  PubMed  Google Scholar 

  • Graves AR, Lewin KA, Lindgren C. 2004. Nitric oxide, cAMP and the biphasic muscarinic modulation of ACh release at the lizard neuromuscular junction. J Physiol 559: 423–432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grozdanovic Z, Baumgarten HG. 1999. Nitric oxide synthase in skeletal muscle fibers: A signaling component of the dystrophin-glycoprotein complex. Histol Hisotpathol 14: 243–256.

    CAS  Google Scholar 

  • Halestrap AP, Price NT. 1999. The proton-linked monocarboxylate transporter (MCT) family: Structure, function and regulation. Biochem J 343(2): 281–299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen MJ, Jovanovska V, Morris MJ. 2004. Adaptive responses in hypothalamic neuropeptide Y in the face of prolonged high-fat feeding in the rat. J Neurochem 88: 909–916.

    Article  CAS  PubMed  Google Scholar 

  • Hasuo H, Akasu T. 2003. Monocarboxylate transporters contribute to the adaptation of neuronal activity to repeated glucose deprivation in the rat lateral septal nucleus. Synapse 49: 97–105.

    Article  CAS  PubMed  Google Scholar 

  • Heimberg H, De Vos A, Moens K, Quartier E, Bouwens L, et al. 1996. The glucose sensor protein glucokinase is expressed in glucagon-producing α-cells. Proc Natl Acad Sci 93: 7036–7041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heller SR, Cryer PE. 1991. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans. Diabetes 40: 223–226.

    Article  CAS  PubMed  Google Scholar 

  • Hevener AL, Bergman RN, Donovan CM. 1997. Novel glucosensor for hypoglycemic detection localized to the portal vein. Diabetes 46: 1521–1525.

    Article  CAS  PubMed  Google Scholar 

  • Hevener AL, Bergman RN, Donovan CM. 2000. Portal afferents are critical for the sympathoadrenal response to hypoglycemia. Diabetes 49: 8–12.

    Article  CAS  PubMed  Google Scholar 

  • Hevener AL, Bergman RN, Donovan CM. 2001. Hypoglycemic detection does not occur in the hepatic artery or liver: Findings consistent with a portal vein glucosensor locus. Diabetes 50: 399–403.

    Article  CAS  PubMed  Google Scholar 

  • Higaki Y, Hirshman MF, Fujii N, Goodyear LJ. 2001. Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle. Diabetes 50: 241–247.

    Article  CAS  PubMed  Google Scholar 

  • Ibrahim N, Bosch MA, Smart JL, Qiu J, Rubinstein M, et al. 2003. Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels. Endocrinology 144: 1331–1340.

    Article  CAS  PubMed  Google Scholar 

  • Iuras A, Telles MM, Bertoncini CRA, Ko GM, de Andrade IS, et al. 2005. Central administration of a nitric oxide precursor abolishes both the hypothalamic serotonin release and the hypophagia induced by interleukin-1[beta] in obese Zucker rats. Regul Pept 124: 145–150.

    Article  CAS  PubMed  Google Scholar 

  • Jetton TL, Liang Y, Pettepher CC, Zimmerman EC, Cox FG, et al. 1994. Analysis of upstream glucokinase promoter activity in transgenic mice and identification of glucokinase in rare neuroendocrine cells in the brain and gut. J Biol Chem 269: 3641–3654.

    Article  CAS  PubMed  Google Scholar 

  • Kang L, Routh VH, Kuzhikandathil EV, Gaspers L, Levin BE. 2004. Physiological and molecular properties of rat hypothalamic ventromedial nucleus glucosensing neurons. Diabetes 53: 559

    Article  Google Scholar 

  • Katz B. 1971. Quantal mechanism of neural transmitter release. Science 173: 123–126.

    Article  CAS  PubMed  Google Scholar 

  • Katz B, Miledi R. 1965. The effect of calcium on acetylcholine release from motor nerve terminals. Proc R Soc Lond B Biol Sci 161: 496–503.

    Article  CAS  PubMed  Google Scholar 

  • Katz B, Miledi R. 1967a. The release of acetylcholine from nerve endings by graded electric pulses. Proc R Soc Lond B Biol Sci 23–38.

    Google Scholar 

  • Katz B, Miledi R. 1967b. The timing of calcium action during neuromuscular transmission. J Physiol 189: 535–544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim EK, Miller I, Aja S, Landree LE, Pinn M, et al. 2004. C75, a Fatty Acid Synthase Inhibitor, Reduces Food Intake via Hypothalamic AMP-activated Protein Kinase. J Biol Chem 279: 19970–19976.

    Article  CAS  PubMed  Google Scholar 

  • Kingwell BA, Formosa M, Muhlmann M, Bradley SJ, McConell GK. 2002. Nitric oxide synthase inhibition reduces glucose uptake during exercise in individuals with type 2 diabetes more than in control subjects. Diabetes 51: 2572–2589.

    Article  CAS  PubMed  Google Scholar 

  • Kow LM, Pfaff DW. 1989. Responses of hypothalamic paraventricular neurons in vitro to norepinephrine and other feeding-relevant agents. Physiol Behav 46: 265–271.

    Article  CAS  PubMed  Google Scholar 

  • Koyama Y, Coker RH, Stone EE, Lacy DB, Jabbour K, et al. 2000. Evidence that carotid bodies play an important role in glucoregulation in vivo. Diabetes 49: 1434–1442.

    Article  CAS  PubMed  Google Scholar 

  • Lam TKT, Pocai A, Gutierrez-Juarez R, Obici S, Bryan J, et al. 2005. Hypothalamic sensing of circulating fatty acids in required for glucose homeostasis. Nat Med 11: 320–327.

    Article  CAS  PubMed  Google Scholar 

  • Laughton JD, Charnay Y, Belloir B, Pellerin L, Magistretti PJ, et al. 2000. Differential messenger RNA distribution of lactate dehydrogenase LDH-1 and LDH-5 isoforms in the rat brain. Neuroscience 96: 619–625.

    Article  CAS  PubMed  Google Scholar 

  • Lee K, Li B, Xi X, Suh Y, Martin RJ. 2005. Role of Neuronal Energy Status in the Regulation of Adenosine 5′-Monophosphate-Activated Protein Kinase, Orexigenic Neuropeptides Expression, and Feeding Behavior. Endocrinology 146: 3–10.

    Article  CAS  PubMed  Google Scholar 

  • Lesniewski LA, Miller TA, Armstrong RB. 2003. Mechanisms of force loss in diabetic mouse skeletal muscle. Muscle Nerve 28: 493–500.

    Article  PubMed  Google Scholar 

  • Levin BE. 2000. Glucose-regulated dopamine release from substantia nigra neurons. Brain Res 874: 158–164.

    Article  CAS  PubMed  Google Scholar 

  • Levin BE, Routh VH. 1996. Role of the brain in energy balance and obesity. Am J Physiol 271: R491–R500.

    CAS  PubMed  Google Scholar 

  • Levin BE, Triscari J, Sullivan AC. 1980. Abnormal sympatho-adrenal function and plasma catecholamines in obese Zucker rats. Pharmacol Biochem Behav 13: 107–113.

    Article  CAS  PubMed  Google Scholar 

  • Li AJ, Ritter S. 2004. Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus. Eur J Neurosci 19: 2147–2154.

    Article  PubMed  Google Scholar 

  • Li J, Hu X, Selvakumar P, Russell RR III, Cushman SW, et al. 2004. Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol 287: E834–E841.

    Article  CAS  Google Scholar 

  • Li S, Pelletier G. 1986. The role of dopamine in the control of neuropeptide Y neurons in the rat arcuate nucleus. Neurosci Lett 69: 74–77.

    Article  CAS  PubMed  Google Scholar 

  • Lindgren CA, Laird MV. 1994. Nitroprusside inhibits neurotransmitter release at the frog neuromuscular junction. Neuroreport 5: 2205–2208.

    Article  CAS  PubMed  Google Scholar 

  • Liu F, Dong Q, Myers AM, Fromm HJ. 1991. Expression of human brain hexokinase in Escherichia coli: Purification and characterization of the expressed enzyme. Biochem Biophys Res Commun 177: 305–311.

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Seino S, Kirchgessner AL. 1999. Identification and characterization of glucoresponsive neurons in the enteric nervous system. J Neurosci 19: 10305–10317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, et al. 2000. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288: 2379–2381.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Barneo J. 2003. Oxygen and glucose sensing by carotid body glomus cells. Curr Opin Neurobiol 13: 493–499.

    Article  CAS  PubMed  Google Scholar 

  • Luck G, Hoch W, Hopf C, Blottner D. 2000. Nitric oxide synthase (NOS-1) coclustered with agrin-induced AChR-specializations on cultured skeletal myotubes. Mol Cell Neurosci 16: 268–281.

    Article  CAS  Google Scholar 

  • Lynch RM, Tompkins LS, Brooks HL, Dunn-Meynell AA, Levin BE. 2000. Localization of glucokinase gene expression in the rat brain. Diabetes 49: 693–700.

    Article  CAS  PubMed  Google Scholar 

  • Maekawa F, Toyoda Y, Torii N, Miwa I, Thompson RC, et al. 2000. Localization of glucokinase-like immunoreactivity in the rat lower brain stem: For possible location of brain glucose-sensing mechanisms. Endocrinology 141: 375–384.

    Article  CAS  PubMed  Google Scholar 

  • Magistretti PJ, Pellerin L. 1996. Cellular mechanisms of brain energy metabolism. Relevance to functional brain imaging and to neurodegenerative disorders. Ann NY Acad Sci 777: 380–387.

    Article  CAS  PubMed  Google Scholar 

  • Magoul R, Onteniente B, Benjelloun W, Tramu G. 1993. Tachykinergic afferents to the rat arcuate nucleus. A combined immunohistochemical and retrograde tracing study. Peptides 14: 275–286.

    Article  CAS  PubMed  Google Scholar 

  • Marques MJ, Santo Neto H. 2005. Acetylcholine receptors and nerve terminal distribution at the neuromuscular junction of non-obese diabetic mice. Anat Rec 267: 112–119.

    Article  Google Scholar 

  • Matschinsky FM, Collins HW. 1997. Essential biochemical design features of the fuel-sensing system in pancreatic beta-cells. Chem Biol 4: 249–257.

    Article  CAS  PubMed  Google Scholar 

  • Matschinsky FM, Glaser B, Magnuson MA. 1998. Pancreatic beta-cell glucokinase: Closing the gap between theoretical concepts and experimental realities. Diabetes 47: 307–315.

    Article  CAS  PubMed  Google Scholar 

  • Mayer J, Thomas DW. 1967. Regulation of food intake and obesity. Science 156: 328–337.

    Article  CAS  PubMed  Google Scholar 

  • McArdle JJ, Sellin LC, Coakley KM, Potian JG, Hognason K. 2006. Mefloquine selectively increases asynchronous acetylcholine release from motor nerve terminals. Neuropharmacology 50(3): 345–353.

    Google Scholar 

  • McKenna MC, Tildon JT, Stevenson JH, Hopkins IB, Huang X, et al. 1998. Lactate transport by cortical synaptosomes from adult rat brain: Characterization of kinetics and inhibitor specificity. Dev Neurosci 20: 300–309.

    Article  CAS  PubMed  Google Scholar 

  • McNay EC, Gold PE. 1999. Extracellular glucose concentrations in the rat hippocampus measured by zero-net-flux: Effects of microdialysis flow rate, strain, and age. J Neurochem 72: 785–790.

    Article  CAS  PubMed  Google Scholar 

  • McNay EC, Fries TM, Gold PE. 2000. Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task. Proc Nat Acad Sci 97: 2881–2885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McNay EC, McCarty RC, Gold PE. 2001. Fluctuations in brain glucose concentration during behavioral testing: Dissociations between brain areas and between brain and blood. Neurobiol Learn Mem 75: 325–337.

    Article  CAS  PubMed  Google Scholar 

  • Miki T, Liss B, Minami K, Shiuchi T, Saraya A, et al. 2001. ATP-sensitive potassium channels in hypothalamic neurons play an essential role in the maintenance of glucose homeostasis by controlling glucagon release and food intake. Nat Neurosci 5: 507–512.

    Article  Google Scholar 

  • Miller I, Ronnett GV, Moran TH, Aja S. 2004. Anorexigenic C75 alters c-Fos in mouse hypothalamic and hindbrain subnuclei. Neuroreport 15: 925–929.

    Article  CAS  PubMed  Google Scholar 

  • Minami T, Shimizu N, Duan S, Oomura Y. 1990. Hypothalamic neuronal activity responses to 3-hydroxybutyric acid, an endogenous organic acid. Brain Res 509: 351–354.

    Article  CAS  PubMed  Google Scholar 

  • Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, et al. 2004. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428: 569–574.

    Article  CAS  PubMed  Google Scholar 

  • Mizuno TM, Makimura H, Silverstein J, Roberts JL, Lopingco T, et al. 1999. Fasting regulates hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocortin in diabetic mice independent of changes in leptin or insulin. Endocrinology 140: 4551–4557.

    Article  CAS  PubMed  Google Scholar 

  • Mizuno Y, Oomura Y. 1984. Glucose responding neurons in the nucleus tractus solitarius of the rat, in vitro study. Brain Res 307: 109–116.

    Article  CAS  PubMed  Google Scholar 

  • Morely JE, Farr SA, Gaskin FS, Kumar VB, Banks WA. 2003. The orexigenic peptides NPY and orexin - A have NO effect on behavior in neuronal-NOS knockout mice. Soc Neurosci Abstr Viewer/Itinerary Planner 615.14.

    Google Scholar 

  • Mulvey C, Harno E, Keenan A, Ohlendieck K. 2005. Expression of the skeletal muscle dystrophin-dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto-Kakizaki rat. Eur J Cell Biol 84: 867–883.

    Article  CAS  PubMed  Google Scholar 

  • Muroya S, Yada T, Shioda S, Takigawa M. 1999. Glucose-sensitive neurons in the rat arcuate nucleus contain neuropeptide Y. Neurosci Lett 264: 113–116.

    Article  CAS  PubMed  Google Scholar 

  • Nakano Y, Oomura Y. 1986. Feeding-related activity of glucose- and morphine-sensitive neurons in the monkey amygdala. Brain Res 399: 167–172.

    Article  CAS  PubMed  Google Scholar 

  • Navarro M, Rodriquez dF, Alvarez E, Chowen JA, Zueco JA, et al. 1996. Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: Evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake. J Neurochem 67: 1982–1991.

    Article  CAS  PubMed  Google Scholar 

  • Obici S, Feng Z, Arduini A, Conti R, Rossetti L. 2003. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 9: 756–761.

    Article  CAS  PubMed  Google Scholar 

  • Oomura Y. 1983. Glucose as a regulator of neuronal activity. Adv Metab Disord 10: 31–65.

    Article  CAS  PubMed  Google Scholar 

  • Oomura Y, Ono H, Ooyama H, Wayner MJ. 1969. Glucose and osmosensitive neurons of the rat hypothalamus. Nature 222: 282–284.

    Article  CAS  PubMed  Google Scholar 

  • Oomura Y, Kimura K, Ooyama H, Maeo T, Iki M, et al. 1964. Reciprocal activities of the ventromedial and lateral hypothalamic area of cats. Science 143: 484–485.

    Article  CAS  PubMed  Google Scholar 

  • Pardal R, Lopez-Barneo J. 2002. Low glucose-sensing cells in the carotid body. Nat Neurosci 5: 197–198.

    Article  CAS  PubMed  Google Scholar 

  • Parkinson JF, Mitrovic B, Merrill JE. 1997. The role of nitric oxide in multiple sclerosis. J Mol Med 75: 174–186.

    Article  CAS  PubMed  Google Scholar 

  • Penicaud L, Ferre P. 1988. Development of insulin resistance during the course of obesity: Lessons from animal models. J Obesity Weight Reg 7: 91–109.

    Google Scholar 

  • Peruzzo B, Pastor FE, Blazquez JL, Schobitz K, Pelaez B, et al. 2000. A second look at the barriers of the medial basal hypothalamus. Exp Brain Res 132: 10–26.

    Article  CAS  PubMed  Google Scholar 

  • Prevot V, DeSeranno S, Estrella C. 2004. Glial-neuronal-endothelial interactions and the neuroendocrine control of GnRH secretion. In: Non-Neuronal Cells of the Nervous System: Function and Dysfunction, Elsevier, Amsterdam pp. 99–214.

    Google Scholar 

  • Prevot V, Croix D, Bouret S, Dutoit S, Tramu G, et al. 1999. Definitive evidence for the existence of morphological plasticity in the external zone of the median eminence during the rat estrous cycle: Implication of neuro-glio-endothelial interactions in gonadotropin-releasing hormone release. Neuroscience 94: 809–819.

    Article  CAS  PubMed  Google Scholar 

  • Puttmann B, Gerlach EM, Kruger M, Blottner D. 2005. Neuromuscular contacts induce nitric oxide signals in skeletal myotubes in vitro. Neurosignals 14: 85–95.

    Article  PubMed  CAS  Google Scholar 

  • Ritter R, Slusser P, Stone S. 1981. Glucoreceptors controlling feeding and blood glucose: Location in the hindbrain. Science 213: 451–452.

    Article  CAS  PubMed  Google Scholar 

  • Ritter S, Bugarith K, Dinh TT. 2001. Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation. J Comp Neurol 432: 197–216.

    Article  CAS  PubMed  Google Scholar 

  • Ritter S, Dinh TT, Zhang Y. 2000. Localization of hindbrain glucoreceptive sites controlling food intake and blood glucose. Brain Res 856: 37–47.

    Article  CAS  PubMed  Google Scholar 

  • Ritter S, Llewellyn-Smith I, Dinh TT. 1998. Subgroups of hindbrain catecholamine neurons are selectively activated by 2-deoxy-D-glucose induced metabolic challenge. Brain Res 805: 41–54.

    Article  CAS  PubMed  Google Scholar 

  • Ritter S, Watts AG, Dinh TT, Sanchez-Watts G, Pedrow C. 2003. Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion. Endocrinology 144: 1357–1367.

    Article  CAS  PubMed  Google Scholar 

  • Rizzo MA, Piston DW. 2003. Regulation of beta cell glucokinase by S-nitrosylation and association with nitric oxide synthase. J Cell Biol 161: 243–248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts CK, Barnard RJ, Scheck SH, Balon TW. 1999. Exercise-stimulated glucose transport in skeletal muscle is nitric oxide dependent. Am J Physiol 273: E220–E225.

    Google Scholar 

  • Roeper J, Ashcroft FM. 2002. Metabolic inhibition and low internal ATP activate K-ATP channels in rat dopaminergic substantia nigra neurones. Pflugers Arch 405: 305–309.

    Google Scholar 

  • Romero-Navarro G, Cabrera-Valladares G, German MS, Matschinsky FM, Velazquez A, et al. 1999. Biotin regulation of pancreatic glucokinase and insulin in primary cultured rat islets and in biotin-deficient rats. Endocrinology 140: 4595–4600.

    Article  CAS  PubMed  Google Scholar 

  • Roncero I, Alvarez E, Vazquez P, Blazquez E. 2000. Functional glucokinase isoforms are expressed in rat brain. J Neurochem 74: 1848–1857.

    Article  CAS  PubMed  Google Scholar 

  • Sanders NM, Ritter S. 2000. Repeated 2-deoxy-D-glucose-induced glucoprivation attenuates Fos expression and glucoregulatory responses during subsequent glucoprivation. Diabetes 49: 1865–1874.

    Article  CAS  PubMed  Google Scholar 

  • Sanders NM, Dunn-Meynell AA, Levin BE. 2004. Third Ventricular Alloxan Reversibly Impairs Glucose Counterregulatory Responses. Diabetes 53: 1230–1236.

    Article  CAS  PubMed  Google Scholar 

  • Santizo RA, Koenig HM, Pelligrino DA. 2001. {beta}-Adrenoceptor and nNOS-derived NO interactions modulate hypoglycemic pial arteriolar dilation in rats. Am J Physiol 280: H562–H568.

    CAS  Google Scholar 

  • Sara Y, Virmani T, Deák F, Liu X, Kavalali ET. 2005. An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission. Neuron 45: 563–573.

    Article  CAS  PubMed  Google Scholar 

  • Sawchenko PE, Swanson RA. 1982. The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat. Brain Res 257: 275–325.

    Article  CAS  PubMed  Google Scholar 

  • Sayegh AI, Covasa M, Ritter RC. 2004. Intestinal infusions of oleate and glucose activate distinct enteric neurons in the rat. Auton Neurosci 115: 54–63.

    Article  CAS  PubMed  Google Scholar 

  • Schiller Y, Rahamimoff R. 1989. Neuromuscular transmission in diabetes: Response to high-frequency activation. J Neurosci 9: 3709–3719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schuit FC, Huypens P, Heimberg H, Pipeleers DG. 2001. Glucose sensing in pancreatic β-cells: A model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus. Diabetes 50: 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Schwartz MW, Baskin DG, Bukowski TR, Kuijper JL, Foster D, et al. 1996. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 45: 531–535.

    Article  CAS  PubMed  Google Scholar 

  • Schwarte RC, Godfrey EW. 2004. Nitric oxide synthase activity is required for postsynaptic differentiation of the embryonic neuromuscular junction. Dev Biol 273: 276–284.

    Article  CAS  PubMed  Google Scholar 

  • Schwartz MW, Sipols AJ, Marks JL, Sanacora G, White JD, et al. 1992. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology 130: 3608–3616.

    Article  CAS  PubMed  Google Scholar 

  • Sheppard DN, Welsh MJ. 1992. Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. J Gen Physiol 100: 573–591.

    Article  CAS  PubMed  Google Scholar 

  • Shimizu N, Oomura Y, Novin D, Grijalva CV, Cooper PH. 1983. Functional correlations between lateral hypothalamic glucose-sensitive neurons and hepatic portal glucose-sensitive units in rat. Brain Res 265: 49–54.

    Article  CAS  PubMed  Google Scholar 

  • Shiraishi T. 1991. Noradrenergic neurons modulate lateral hypothalamic chemical and electrical stimulation induced feeding. Brain Res Bull 27: 347–351.

    Article  CAS  PubMed  Google Scholar 

  • Shoji S. 1992. Glucose regulation of synaptic transmission in the dorsolateral septal nucleus of the rat. Synapse 12: 322–332.

    Article  CAS  PubMed  Google Scholar 

  • Silinsky EM. 2004. Adenosine decreases both presynaptic calcium currents and neurotransmitter release at the mouse neuromuscular junction. J Physiol 558: 389–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silver IA, Erecinska M. 1994. Extracellular glucose concentration in mammalian brain: Continuous monitoring of changes during increased neuronal activity and upon limitation in oxygen supply in normo-, hypo, and hyperglycemic animals. J Neurosci 14: 5068–5076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silver IA, Erecinska M. 1998. Glucose-induced intracellular ion changes in sugar-sensitive hypothalamic neurons. J Neurophysiol 79: 1733–1745.

    Article  CAS  PubMed  Google Scholar 

  • Simpson IA, Appel NM, Hokari M, Oki J, Holman GD, et al. 1999. Blood-brain barrier glucose transporter: Effects of hypo- and hyperglycemia revisited. J Neurochem 72: 238–247.

    Article  CAS  PubMed  Google Scholar 

  • Sindelar DK, Marie L, Miura GI, Palmiter RD, McMinn JE, et al. 2004. Neuropeptide Y Is Required for Hyperphagic Feeding in Response to Neuroglucopenia. Endocrinology 145: 3363–3368.

    Article  CAS  PubMed  Google Scholar 

  • Song Z, Routh VH. 2005a. Recurrent hypoglycemia reduces the glucose sensitivity of glucose sensing neurons in the ventromedial hypothalamic nucleus (VMN). 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2005. Online. 532.9.

    Google Scholar 

  • Song Z, Routh VH. 2005b. Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes 54: 15–22.

    Article  CAS  PubMed  Google Scholar 

  • Song Z, Routh VH. 2006. Recurrent hypoglycemia decreases the glucose sensitivity of glucose-inhibited (G1) neurons in the ventromedial hypothalamic nucleus (VMN). Am J Physiol Regul Integr Comp Physiol Jun 22 (epub ahead of print) doi: 10.1152/ajpregu 00148.2006.

    Google Scholar 

  • Song Z, Levin BE, McArdle JJ, Bakhos N, Routh VH. 2001. Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes 50: 2673–2681.

    Article  CAS  PubMed  Google Scholar 

  • Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford MLJ. 1997. Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 390: 521–525.

    Article  CAS  PubMed  Google Scholar 

  • Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford MLJ. 2000. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 3: 757–758.

    Article  CAS  PubMed  Google Scholar 

  • Stanley BG, Anderson KC, Grayson MH, Leibowitz SF. 1989. Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats. Physiol Behav 46: 173–177.

    Article  CAS  PubMed  Google Scholar 

  • Steffens AB, Mogenson GJ, Stevenson JA. 1972. Blood glucose, insulin, and free fatty acids after stimulation and lesions of the hypothalamus. Am J Physiol 222: 1446–1452.

    Article  CAS  PubMed  Google Scholar 

  • Steffens AB, Scheurink AJ, Luiten PG, Bohus B. 1988. Hypothalamic food intake regulating areas are involved in the homeostasis of blood glucose and plasma FFA levels. Physiol Behav 44: 581–589.

    Article  CAS  PubMed  Google Scholar 

  • Stoddard-Apter SL, Bergdall VK, Townsend DW, Levin BE. 1986. Plasma catecholamines associated with hypothalamically-elicited defense behavior. Physiol Behav 36: 867–873.

    Article  Google Scholar 

  • Tache Y, Yang H, Kaneko H. 1995. Caudal raphe-dorsal vagal complex peptidergic projections: Role in gastric vagal control. Peptides 16: 431–435.

    Article  CAS  PubMed  Google Scholar 

  • Tews DS. 2001. Role of nitric oxide and nitric oxide synthases in experimental models of denervation and reinnervation. Microsc Res Tech 55: 181–186.

    Article  CAS  PubMed  Google Scholar 

  • Thomas S, Robitaille R. 2001. Differential Frequency-Dependent Regulation of Transmitter Release by Endogenous Nitric Oxide at the Amphibian Neuromuscular Synapse. J Neurosci 21: 1087–1095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thor K, Helke CJ. 2002. Serotonin and substance P colocalization in medullary projections to the nucleus tractus solitarius: Dual-colour immunohistochemistry combined with retrograde tracing. J Chem Neuroanat 2: 139–148.

    Google Scholar 

  • Thornton JE, Cheung CC, Clifton DK, Steiner RA. 1997. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 138: 5063–5066.

    Article  CAS  PubMed  Google Scholar 

  • Thupari JN, Landree LE, Ronnett GV, Kuhajda FP. 2002. C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc Natl Acad Sci 99: 9498–9502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsacopoulos M, Magistretti PJ. 1996. Metabolic coupling between glia and neurons. J Neurosci 16: 877–885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tseng C, Huang S, Lo W, Lin C, Hsiao M. 2003. Insulin molecular signaling is defective in NTS neurons of adult spontaneous hypertensive rat. Society for Neuroscience Abstract Viewer/Itinerary Planner 922.1.

    Google Scholar 

  • Tsuura Y, Ishida H, Shinomura T, Nishimura M, Seino Y. 1998. Endogenous nitric oxide inhibits glucose-induced insulin secretion by suppression of phosphofructokinase activity in pancreatic islets. Biochem Biophys Res Commun 252: 34–38.

    Article  CAS  PubMed  Google Scholar 

  • Tu Y, Thupari JN, Kim EK, Pinn ML, Moran TH, et al. 2005. C75 Alters Central and Peripheral Gene Expression to Reduce Food Intake and Increase Energy Expenditure. Endocrinology 146: 486–493.

    Article  CAS  PubMed  Google Scholar 

  • Tucker DC, Saper CB, Ruggiero DA, Reis DJ. 1987. Organization of central adrenergic pathways: I. Relationships of ventrolateral medullary projections to the hypothalamus and spinal cord. J Comp Neurol 259: 591–603.

    Article  CAS  PubMed  Google Scholar 

  • Vamecq J, Vallee L, Lesage F, Gressens P, Stables JP. 2005. Antiepileptic popular ketogenic diet: Emerging twists in an ancient story. Prog Neurobiol 75: 1–28.

    Article  CAS  PubMed  Google Scholar 

  • Van der Kloot W. 2003. Loading and recycling of synaptic vesicles in the Torpedo electric organ and the vertebrate neuromuscular junction. Prog Neurobiol 71: 269–303.

    Article  CAS  PubMed  Google Scholar 

  • van Dijk G, Bottone AE, Strubbe JH, Steffens AB. 1994. Hormonal and metabolic effects of paraventricular hypothalamic administration of neuropeptide Y during rest and feeding. Brain Res 660: 96–103.

    Article  CAS  PubMed  Google Scholar 

  • Vannucci SJ, Hagberg H. 2004. Hypoxia-ischemia in the immature brain. J Exp Biol 207: 3149–3154.

    Article  CAS  PubMed  Google Scholar 

  • Villarroel A, Sakmann B. 1996. Calcium permeability increase of endplate channels in rat muscle during postnatal development. J Physiol 496: 331–338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang R, Liu X, Hentges ST, Dunn-Meynell AA, Levin BE, et al. 2004. The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides. Diabetes 53: 1959–1965.

    Article  CAS  PubMed  Google Scholar 

  • Wang R, Cruciani-Guglielmacci C, Migrenne S, Magnan C, Cotero VE, et al. 2006. The effects of oleic-acid (OA) on distinct populations of neurons in the hypothalamic arcuate nucleus (ARC) are dependent on extracellular glucose levels. J Neurophysiol 95(3): 1491–1498.

    Google Scholar 

  • White JD. 1993. Neuropeptide Y: A central regulator of energy homeostasis. Regul Pept 49: 93–107.

    Article  CAS  PubMed  Google Scholar 

  • Winter MC, Sheppard DN, Carson MR, Welsh MJ. 1994. Effect of ATP concentration on CFTR Cl- channels: A kinetic analysis of channel regulation. Biophys J 66: 1398–1403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang XJ, Kow LM, Funabashi T, Mobbs CV. 1999. Hypothalamic glucose sensor: Similarities to and differences from pancreatic beta-cell mechanisms. Diabetes 48: 1763–1772.

    Article  CAS  PubMed  Google Scholar 

  • Yang XJ, Kow LM, Pfaff DW, Mobbs CV. 2004. Metabolic Pathways That Mediate Inhibition of Hypothalamic Neurons by Glucose. Diabetes 53: 67–73.

    Article  CAS  PubMed  Google Scholar 

  • Yoshimatsu H, Niijima A, Oomura Y, Yawabe K, Katafuchi T. 1984. Effects of hypothalamic lesion on pancreatic autonomic nerve activity in the rat. Brain Res 303: 147–152.

    Article  CAS  PubMed  Google Scholar 

  • Zawar C, Neumcke B. 2000. Differential activation of ATP-sensitive potassium channels during energy depletion in CA1 pyramidal cells and interneurones of rat hippocampus. Pfugers Arch 439: 256–262.

    Article  CAS  Google Scholar 

  • Zhu X, Heunks LM, Ennen L, Machiels HA, Van Der Heijden HF et al. 2006. Nitric oxide modulates neuromuscular transmission during hypoxia in rat diaphragm. Muscle Nerve 33: 104–112.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported, in part, by DK55619 (VHR), DK64566 (VHR), American Diabetes Association Junior Faculty Award (NMS), NS045979 (JJM), and the Kirby Foundation (JJM).

Authors
  1. V. H Routh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. J. McArdle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. M. Sanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Z. Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha (Director) (Director)

  2. University of Tennessee Health Science Center, 62 South Dunlap, 38163, Memphis, Tennessee, USA

    Dianna A. Johnson (Hiatt Professor of Ophthalmology Associate Vice Chancellor for Academic, Faculty and Student Affairs) (Hiatt Professor of Ophthalmology Associate Vice Chancellor for Academic, Faculty and Student Affairs)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this entry

Cite this entry

Routh, V.H., McArdle, J.J., Sanders, N.M., Song, Z., Wang, R. (2007). Glucose Sensing Neurons. In: Lajtha, A., Johnson, D.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30374-1_7

Download citation

Publish with us

Policies and ethics

Search

Navigation