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Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

By Sabine D. Jordan, A. Christine Könner and Jens C. Brüning

Abstract

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus

Topics: Review
Publisher: SP Birkhäuser Verlag Basel
OAI identifier: oai:pubmedcentral.nih.gov:2933848
Provided by: PubMed Central

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Citations

  1. (1855) Lec ¸ons de physiologie experimentale applique ´ea ` la medecine. Baille `re et Fils
  2. (1990). A 48-hour lipid infusion in the rat timedependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation.
  3. (2004). A new ATP-sensitive K? channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus.
  4. (2006). A POMC variant implicates beta-melanocytestimulating hormone in the control of human energy balance.
  5. (2001). A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans.
  6. (2005). A role for hypothalamic malonyl-CoA in the control of food intake.
  7. (2009). A role for the CREB co-activator CRTC2 in the hypothalamic mechanisms linking glucose sensing with gene regulation.
  8. (2005). Activation of ATPsensitive K? channels in the ventromedial hypothalamus amplifies counterregulatory hormone responses to hypoglycemia in normal and recurrently hypoglycemic rats.
  9. (1964). Activity of single neurons in the hypothalamic feeding centers: effect of glucose.
  10. (2008). Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice.
  11. (2005). Agouti-related peptideexpressing neurons are mandatory for feeding.
  12. (2007). Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism.
  13. (2009). AMP-activated protein kinase and nitric oxide regulate the glucose sensitivity of ventromedial hypothalamic glucoseinhibited neurons.
  14. (2004). AMP-activated protein kinase plays a role in the control of food intake.
  15. (2006). AMP-activated protein kinase—development of the energy sensor concept.
  16. (2005). AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism.
  17. (2004). AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus.
  18. (2007). AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons.
  19. (1994). Analysis of upstream glucokinase promoter activity in transgenic mice and identification of glucokinase in rare neuroendocrine cells in the brain and gut.
  20. (1997). Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein.
  21. (1999). ATP-sensitive K? channels and insulin secretion: their role in health and disease.
  22. (2001). ATP-sensitive K? channels in the hypothalamus are essential for the maintenance of glucose homeostasis.
  23. (2007). ATP-sensitive K(?) channels regulate the release of GABA in the ventromedial hypothalamus during hypoglycemia.
  24. (1996). Banting Lecture
  25. (2004). Beta oxidation in the brain is required for the effects of non-esterified fatty acids on glucose-induced insulin secretion in rats.
  26. (2006). Blockade of GABA(A) receptors in the ventromedial hypothalamus further stimulates glucagon and sympathoadrenal but not the hypothalamo-pituitary-adrenal response to hypoglycemia.
  27. (2006). Blood–brain barrier and energy balance.
  28. (2007). Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins.
  29. (2007). Brain glucose sensing, counterregulation, and energy homeostasis. Physiology (Bethesda)
  30. (2003). C75 inhibits food intake by increasing CNS glucose metabolism.
  31. (2000). Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy.
  32. (2002). Central administration of oleic acid inhibits glucose production and food intake.
  33. (2006). Central insulin action in energy and glucose homeostasis.
  34. (2008). Central insulin action regulates peripheral glucose and fat metabolism in mice.
  35. (2000). Central nervous system control of food intake.
  36. (2007). Characterization of glucosensing neuron subpopulations in the arcuate nucleus: integration in neuropeptide Y and pro-opio melanocortin networks?
  37. (1994). Characterization of the influence of unsaturated free fatty acids on brain GABA/benzodiazepine receptor binding in vitro.
  38. (1998). Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area.
  39. (1979). Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons.
  40. (1993). Chronic intrahypothalamic insulin infusion in the rat: behavioral specificity.
  41. (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.
  42. (2005). Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes.
  43. (2005). Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus.
  44. (2004). Consumption of a high-fat diet alters the homeostatic regulation of energy balance.
  45. (2009). Control of energy homeostasis by insulin and leptin: targeting the arcuate nucleus and beyond.
  46. (1993). Counterregulation during hypoglycemia is directed by widespread brain regions.
  47. (1981). D-glucose infusions into the basal ventromedial hypothalamus and feeding.
  48. (1986). D-glucose suppression of eating after intra-third ventricle infusion in rat.
  49. (2005). Diabetes, obesity, and the brain.
  50. (2007). Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons.
  51. (2005). Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleus.
  52. (2004). Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain—an immunohistochemical study.
  53. (1998). Distribution and phenotype of neurons containing the ATP-sensitive K? channel in rat brain.
  54. (2003). Distribution of glucokinase, glucose transporter GLUT2, sulfonylurea receptor-1, glucagon-like peptide-1 receptor and neuropeptide Y messenger RNAs in rat brain by quantitative real-time RT-PCR.
  55. (2004). Diverse causes of hypoglycemia-associated autonomic failure in diabetes.
  56. (2002). Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(?) channels.
  57. (2002). Effect of a fatty acid synthase inhibitor on food intake and expression of hypothalamic neuropeptides.
  58. (1975). Effect of free fatty acid on the rat lateral hypothalamic neurons.
  59. (2003). Effect of the anorectic fatty acid synthase inhibitor C75 on neuronal activity in the hypothalamus and brainstem.
  60. (2009). Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons.
  61. (2006). Effects of oleic acid on distinct populations of neurons in the hypothalamic arcuate nucleus are dependent on extracellular glucose levels.
  62. (2005). Effects of unsaturated fatty acids on calcium-activated potassium current in gastric myocytes of guinea pigs.
  63. (2008). El-Sohemy A
  64. (2009). Enhanced hypothalamic glucose sensing in obesity: alteration of redox signaling.
  65. (2006). Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity.
  66. (2006). Evidence from glut2-null mice that glucose is a critical physiological regulator of feeding.
  67. (1996). Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice.
  68. (1994). expression in specific brain nuclei.
  69. (2002). Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment.
  70. (1980). Fall in blood glucose level precedes meal onset in free-feeding rats.
  71. (2009). Fasting enhances the response of arcuate neuropeptide Y-glucose-inhibited neurons to decreased extracellular glucose.
  72. (2005). Fatty acid metabolism as a target for obesity treatment.
  73. (2007). Fatty acid sensing and nervous control of energy homeostasis.
  74. (1997). Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels.
  75. (2006). Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake.
  76. (2009). Fuel utilization by hypothalamic neurons: roles for ROS. Trends Endocrinol Metab
  77. (1953). Genetic, traumatic and environmental factors in the etiology of obesity.
  78. (2006). Ghrelin action in the brain controls adipocyte metabolism.
  79. (2008). Ghrelin raises [Ca2 ?]i via AMPK in hypothalamic arcuate nucleus NPY neurons.
  80. (2000). Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans.
  81. (2006). Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing.
  82. (2002). Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons.
  83. (2007). Glucokinase regulates reproductive function, glucocorticoid secretion, food intake, and hypothalamic gene expression.
  84. (1981). Glucoreceptors controlling feeding and blood glucose: location in the hindbrain.
  85. (1969). Glucose and osmosensitive neurones of the rat hypothalamus.
  86. (1991). Glucose increases rat plasma norepinephrine levels by direct action on the brain.
  87. (1984). Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells.
  88. (1974). Glucose inhibition of the glucose-sensitive neurone in the rat lateral hypothalamus.
  89. (2009). Glucose inhibition persists in hypothalamic neurons lacking tandem-pore K? channels.
  90. (2007). Glucose sensing by hypothalamic neurones and pancreatic islet cells: AMPle evidence for common mechanisms? Exp Physiol 92:311–319
  91. (2007). Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity.
  92. (2001). Glucose sensing in pancreatic beta-cells: a model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus.
  93. (1990). Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K? channels.
  94. (1998). Glucose-induced intracellular ion changes in sugar-sensitive hypothalamic neurons.
  95. (1987). Glucose-induced norepinephrine levels and obesity resistance.
  96. (1989). Glucose-induced sympathetic activation in obesity-prone and resistant rats.
  97. (1987). Glucose, insulin and sympathoadrenal activation.
  98. (1990). Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K? channels.
  99. (1999). Glucosesensitive neurons in the rat arcuate nucleus contain neuropeptide Y.
  100. (1953). Glucostatic mechanism of regulation of food intake.
  101. (1999). Gut vagal afferent lesions increase meal size but do not block gastric preload-induced feeding suppression.
  102. (2007). H2O2 signaling in the nigrostriatal dopamine pathway via ATP-sensitive potassium channels: issues and answers. Antioxid Redox Signal 9:219–231
  103. (1973). Hasselblatt A
  104. (1991). Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction.
  105. (1997). Histological markers of neuronal, axonal and astrocytic changes after lateral rigid impact traumatic brain injury.
  106. (2009). Hormone and glucose signalling in POMC and AgRP neurons.
  107. (2007). Hyperglycemia impairs glucose and insulin regulation of nitric oxide production in glucose-inhibited neurons in the ventromedial hypothalamus.
  108. (1998). Hypocretin/orexin- and melanin-concentrating hormoneexpressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems.
  109. (2010). Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism.
  110. (2004). Hypothalamic ATPsensitive K? channels play a key role in sensing hypoglycemia and triggering counterregulatory epinephrine and glucagon responses.
  111. (2008). Hypothalamic CaMKK2 contributes to the regulation of energy balance.
  112. (2003). Hypothalamic ependymal-glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing.
  113. (1999). Hypothalamic glucose sensor: similarities to and differences from pancreatic beta-cell mechanisms.
  114. (2008). Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity.
  115. (2002). Hypothalamic insulin signaling is required for inhibition of glucose production.
  116. (2005). Hypothalamic K(ATP) channels control hepatic glucose production.
  117. (2003). Hypothalamic malonyl-CoA as a mediator of feeding behavior.
  118. (2006). Hypothalamic mTOR signaling regulates food intake.
  119. (2008). Hypothalamic orexins/hypocretins as regulators of breathing. Expert Rev Mol Med
  120. (2009). Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet.
  121. (2003). Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels.
  122. (2004). Hypothalamic responses to long-chain fatty acids are nutritionally regulated.
  123. (2005). Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis.
  124. (2008). Hypothalamic sensing of circulating lactate regulates glucose production.
  125. (2005). Hypothalamic sensing of fatty acids.
  126. (1996). Identification of targets of leptin action in rat hypothalamus.
  127. (2004). Immunocytochemical localization of the glucose transporter 2 (GLUT2) in the adult rat brain. II. Electron microscopic study.
  128. (2003). Immunolesion of norepinephrine and epinephrine afferents to medial hypothalamus alters basal and 2-deoxy-D-glucose-induced neuropeptide Y and agouti generelated protein messenger ribonucleic acid expression in the arcuate nucleus.
  129. (2001). Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation.
  130. (2004). In vitro increase in intracellular calcium concentrations induced by low or high extracellular glucose levels in ependymocytes and serotonergic neurons of the rat lower brainstem.
  131. (2001). In vivo fatty acid incorporation into brain phosholipids in relation to plasma availability, signal transduction and membrane remodeling.
  132. (1996). In vivo labeling of brain phospholipids by long-chain fatty acids: relation to turnover and function.
  133. (2008). Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia.
  134. (2007). Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56:1647–1654
  135. (1991). Influence of fatty acid oxidation in lateral hypothalamus on food intake and body composition.
  136. (1977). Ingestive behavior after intracerebral and intracerebroventricular infusions of glucose and 2-deoxy-D-glucose.
  137. (2007). Inhibition by glucose or leptin of hypothalamic neurons expressing neuropeptide Y requires changes in AMP-activated protein kinase activity.
  138. (2003). Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production.
  139. (1990). Inhibition of Na, K-ATPase and sodium pump by protein kinase C regulators sphingosine, lysophosphatidylcholine, and oleic acid.
  140. (2007). Insulin action in AgRPexpressing neurons is required for suppression of hepatic glucose production.
  141. (2003). Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia.
  142. (2009). Insulin blunts the response of glucose-excited neurons in the ventrolateral-ventromedial hypothalamic nucleus to decreased glucose.
  143. (2009). Integrative neurobiology of energy homeostasis-neurocircuits, signals and mediators.
  144. (2001). Intracellular signalling. Key enzyme in leptin-induced anorexia.
  145. (1998). Intracerebroventricular administration of antisense oligodeoxynucleotide against GLUT2 glucose transporter mRNA reduces food intake, body weight change and glucoprivic feeding response in rats.
  146. (1988). Intracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity.
  147. (2000). Involvement of adenosine triphosphate-sensitive K? channels in glucose-sensing in the rat solitary tract nucleus.
  148. (2006). Islet beta cell failure in type 2 diabetes.
  149. (2004). Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K-dependent actin reorganization and KATP channel activation.
  150. (1997). Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels.
  151. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.
  152. (2002). Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase.
  153. (1995). Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone release.
  154. (1997). Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats.
  155. (2000). Localization of glucokinase gene expression in the rat brain.
  156. (2000). Localization of glucokinase-like immunoreactivity in the rat lower brain stem: for possible location of brain glucose-sensing mechanisms.
  157. (2000). Localization of hindbrain glucoreceptive sites controlling food intake and blood glucose.
  158. (2002). Localization of messenger RNAs encoding enzymes associated with malonyl-CoA metabolism in mouse brain.
  159. (2002). Long-chain polyunsaturated fatty acid accretion in brain.
  160. (1994). Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle.
  161. (2006). Lorsignol A
  162. (1994). Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing.
  163. (2008). Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes.
  164. (1998). Membrane phospholipid control of nucleotide sensitivity of KATP channels.
  165. (2008). Metabolism-independent sugar sensing in central orexin neurons.
  166. (2006). Mitochondrial reactive oxygen species are required for hypothalamic glucose sensing.
  167. (1984). Neural network of glucose monitoring system.
  168. (2008). Neurocircuits integrating hormone and nutrient signaling in control of glucose metabolism.
  169. (1984). Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats.
  170. (1984). Neuropeptide Y: stimulation of feeding and drinking by injection into the paraventricular nucleus.
  171. (2005). NPY/ AgRP neurons are essential for feeding in adult mice but can be ablated in neonates.
  172. (2007). NPY/AgRP neurons are not essential for feeding responses to glucoprivation.
  173. (2002). Nucleotides and phospholipids compete for binding to the C terminus of KATP channels.
  174. (2003). Obesity-induced inflammatory changes in adipose tissue.
  175. (1985). On-line continuous measurement of blood glucose and meal pattern in free-feeding rats: the role of glucose in meal initiation.
  176. (1999). Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells.
  177. (2001). Overfeeding rapidly induces leptin and insulin resistance.
  178. (2009). Ozcan U
  179. (1997). Pathways of Fos expression in locus ceruleus, dorsal vagal complex, and PVN in response to intestinal lipid.
  180. (2008). PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response.
  181. (1997). Peroxide modulation of slow onset potentiation in rat hippocampus.
  182. (2007). Pharmacological and molecular characterization of ATP-sensitive K(?) conductances in CART and NPY/AgRP expressing neurons of the hypothalamic arcuate nucleus.
  183. (2004). Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neurons.
  184. (1998). PIP2 and PIP as determinants for ATP inhibition of KATP channels.
  185. (2000). PKAand arachidonic acidactivationofhuman recombinantClC-2 chloride channels.
  186. (1994). Positional cloning of the mouse obese gene and its human homologue.
  187. (1978). Projections from the nucleus of the solitary tract in the rat.
  188. (2000). Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors.
  189. (1998). Reduced glucose-induced neuronal activation in the hypothalamus of diet-induced obese rats.
  190. (2005). Regulation of blood glucose by hypothalamic pyruvate metabolism.
  191. (2005). Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors.
  192. (2009). required for development of fatty acid-induced leptin resistance and diet-induced obesity.
  193. (2007). Role for mitochondrial reactive oxygen species in brain lipid sensing: redox regulation of food intake.
  194. (1989). Role of brain in counterregulation of insulin-induced hypoglycemia in dogs.
  195. (2000). Role of brain insulin receptor in control of body weight and reproduction.
  196. (1997). Role of melanocortinergic neurons in feeding and the agouti obesity syndrome.
  197. Ronnett GV (2004) C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMPactivated protein kinase.
  198. (2009). Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity.
  199. (2001). Saturated fatty acids, but not unsaturated fatty acids, induce the expression of 3272
  200. (2001). Selective deletion of leptin receptor in neurons leads to obesity.
  201. (2009). Small decrements in systemic glucose provoke increases in hypothalamic blood flow prior to the release of counterregulatory hormones.
  202. (1998). Subgroups of hindbrain catecholamine neurons are selectively activated by 2-deoxy-D-glucose induced metabolic challenge.
  203. (2003). Suppression of calcium sparks in rat ventricular myocytes and direct inhibition of sheep cardiac RyR channels by EPA, DHA and oleic acid.
  204. (1984). Suppression of food intake by intravenous nutrients and insulin in the baboon.
  205. (1981). Sustained intracerebroventricular infusion of brain fuels reduces body weight and food intake in rats.
  206. (2009). Sweet taste signaling functions as a hypothalamic glucose sensor.
  207. (1988). Sympathetic activity following paraventricular injections of glucose and insulin.
  208. (2007). Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia.
  209. (1997). The AMP-activated protein kinase—fuel gauge of the mammalian cell?
  210. (2008). The CAMplexities of central ghrelin.
  211. (2003). The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.
  212. (1987). The effect of intrahypothalamic injections of glucose on sympathetic efferent firing rate.
  213. (1994). The human melanocyte stimulating hormone receptor has evolved to become ‘‘super-sensitive’’ to melanocortin peptides.
  214. (1993). The prohormone convertases PC1 and PC2 mediate distinct endoproteolytic cleavages in a strict temporal order during proopiomelanocortin biosynthetic processing.
  215. (2004). The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides.
  216. (2008). The role for endoplasmic reticulum stress in diabetes mellitus.
  217. (2005). The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 16:59–
  218. (2000). The role of long-chain fatty acids in regulating food intake and cholecystokinin release in humans.
  219. (1984). Thermic effect of glucose in man. Obligatory and facultative thermogenesis.
  220. (1990). Tolbutamide excites rat glucoreceptive ventromedial hypothalamic neurones by indirect inhibition of ATP-K? channels.
  221. (2000). Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion.
  222. Tschop MH, GrutersA,Krude H(2006)A rolefor beta-melanocyte-stimulating hormone in human body-weight regulation.CellMetab 3:141–146
  223. (2000). Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity.
  224. (2008). UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals.
  225. (1987). Utilization of plasma fatty acid in rat brain: distribution of [14C]palmitate between oxidative and synthetic pathways.
  226. (2006). Verkhratsky A
  227. (2008). Vidal-Puig A
  228. (1981). Woods SC