Glucose sensing during hypoglycemia: Lessons from the lab

Diabetes Care

Volumn 32, Issue 8, 2009, Pages 1357-1363

  McCrimmon, Rory ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; GLUCOSE TRANSPORTER; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; NEUROHORMONE; NEUROTRANSMITTER; NITRIC OXIDE;

ADRENERGIC SYSTEM; BLOOD BRAIN BARRIER; BRAIN REGION; CEREBROSPINAL FLUID; CHOLINERGIC SYSTEM; DISEASE DURATION; DOWN REGULATION; ENZYME ACTIVITY; GLUCOSE UTILIZATION; HUMAN; HYPOGLYCEMIA; HYPOTHALAMUS VENTROMEDIAL NUCLEUS; INSULIN DEPENDENT DIABETES MELLITUS; NERVE CELL NETWORK; NEUROTRANSMISSION; REVIEW; STRESS;

ADENYLATE KINASE; ANIMALS; AWARENESS; DIABETES MELLITUS, TYPE 1; DISEASE MODELS, ANIMAL; GASTROINTESTINAL TRACT; HUMANS; HYPOGLYCEMIA; INSULIN; INSULIN-SECRETING CELLS; NEURONS; VENTROMEDIAL HYPOTHALAMIC NUCLEUS;

EID: 68149092028     PISSN: 01495992     EISSN: 19355548     Source Type: Journal    
DOI: 10.2337/dc09-0123     Document Type: Review

References (59)

1. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50:1140-1147
2. Mokan M, Mitrakou A, Veneman T, Ryan C, Korytkowski M, Cryer P, Gerich J. Hypoglycemia unawareness in IDDM. Diabetes Care 1994;17:1397-1403
3. McCrimmon R. The mechanisms that underlie glucose sensing during hypoglycaemia in diabetes. Diabet Med 2008;25: 513-522 (Pubitemid 351590875)
4. McNay EC, Gold PE. Extracellular glucose concentrations in the rat hippocampus measured by zero-net-flux: effects of microdialysis flow rate, strain, and age (Letter). Journal of Neurochemistry 1999; 72:785-790
5. Borg WP, During MJ, Sherwin RS, Borg MA, Brines ML, Shulman GI. Ventromedial hypothalamic lesions in rats suppress counterregulatory responses to hypoglycemia. J Clin Invest 1994;93:1677-1682 (Pubitemid 24116408)
6. Borg WP, Sherwin RS, During MJ, Borg MA, Shulman GI. Local ventromedial hypothalamus glucopenia triggers counter-regulatory hormone release. Diabetes 1995;44:180-184
7. Borg MA, Sherwin RS, Borg WP, Tamborlane WV, Shulman GI. Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats. J Clin Invest 1997;99:361-365
8. Routh VH. Glucose-sensing neurons: are they physiologically relevant? Physiol Behav 2002;76:403-413
9. Kang L, Routh VH, Kuzhikandathil EV, Gaspers LD, Levin BE. Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neurons. Diabetes 2004;53:549-559 (Pubitemid 38270622)
10. Tong Q, Ye C, McCrimmon RJ, Dhillon H, Choi B, Kramer MD, Yu J, Yang Z, Christiansen LM, Lee CE, Choi CS, Zigman JM, Shulman GI, Sherwin RS, Elmquist JK, Lowell BB. Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia. Cell Metab 2007;5:383-393 (Pubitemid 46667758)
11. Buijs RM, Chun SJ, Niijima A, Romijn HJ, Nagai K. Parasympathetic and sympathetic control of the pancreas: a role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake. J Comp Neurol 2001;431:405-423 (Pubitemid 32178945)
12. Saberi M, Bohland M, Donovan CM. The locus for hypoglycemic detection shifts with the rate of fall in glycemia: the role of portal-superior mesenteric vein glucose sensing. Diabetes 2008;57: 1380-1386
13. Fujita S, Bohland M, Sanchez-Watts G, Watts AG, Donovan CM. Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons. Am J Physiol Endocrinol Metab 2007;293:E96-E101
14. Song Z, Levin BE, McArdle JJ, Bakhos N, Routh VH. Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes 2001;50:2673-2681 (Pubitemid 33733117)
15. Oomura Y, Ono T, Ooyama H, Wayner MJ. Glucose and osmosensitive neurones of the rat hypothalamus. Nature 1969; 222:282-284
16. Magistretti PJ, Sorg O, Naichen Y, Pellerin L, de Rham S, Martin JL. Regulation of astrocyte energy metabolism by neurotransmitters. Ren Physiol Biochem 1994; 17:168-171 (Pubitemid 24114782)
17. Borg MA, Tamborlane WV, Shulman GI, Sherwin RS. Local lactate perfusion of the ventromedial hypothalamus suppresses hypoglycemic counterregulation. Diabetes 2003;52:663-666
18. Kennedy HJ, Pouli AE, Ainscow EK, Jouaville LS, Rizzuto R, Rutter GA. Glucose generates sub-plasma membrane ATP microdomains in single islet beta-cells: potential role for strategically located mitochondria. J Biol Chem 1999;274: 13281-13291 (Pubitemid 129518536)
19. Sherwin RS. Bringing light to the dark side of insulin: a journey across the blood-brain barrier. Diabetes 2008;57:2259-2268
20. Yang XJ, Kow LM, Funabashi T, Mobbs CV. Hypothalamic glucose sensor: similarities to and differences from pancreatic β-cell mechanisms. Diabetes 1999;48: 1763-1772 (Pubitemid 29415195)
21. Kang L, Dunn-Meynell AA, Routh VH, Gaspers LD, Nagata Y, Nishimura T, Eiki J, Zhang BB, Levin BE. Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes 2006;55:412-420 [erratum appears in Diabetes 2006;55:862] (Pubitemid 43343271)
22. Levin BE, Becker TC, Eiki J, Zhang BB, Dunn-Meynell AA. Ventromedial hypothalamic glucokinase is an important mediator of the counterregulatory response to insulin-induced hypoglycemia. Diabetes 2008;57:1371-1379
23. Ashford ML, Boden PR, Treherne JM. Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. Pflugers Arch 1990; 415:479-483
24. Ashford ML, Boden PR, Treherne JM. Tolbutamide excites rat glucoreceptive ventromedial hypothalamic neurones by indirect inhibition of ATP-K+ channels. Br J Pharmacol 1990;101:531-540
25. Miki T, Liss B, Minami K, Shiuchi T, Saraya A, Kashima Y, Horiuchi M, Ashcroft F, Minokoshi Y, Roeper J, Seino S. ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis (Letter). Nat Neurosci 2001;4:507-512 (Pubitemid 32397188)
26. + channels play a key role in sensing hypoglycemia and triggering counter-regulatory epinephrine and glucagon responses. Diabetes 2004;53:2542-2551
27. + channels in the ventromedial hypothalamus amplifies counterregulatory hormone responses to hypoglycemia in normal and recurrently hypoglycemic rats. Diabetes 2005;54:3169-3174
28. McNay EC, Gold PE. Age-related differences in hippocampal extracellular fluid glucose concentration during behavioral testing and following systemic glucose administration. J Gerontol Series A Biol Sci Med Sci 2001;56:B66-B71
29. Abi-Saab WM, Maggs DG, Jones T, Jacob R, Srihari V, Thompson J, Kerr D, Leone P, Krystal JH, Spencer DD, During MJ, Sherwin RS. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. J Cereb Blood Flow Metab 2002;22:271-279 (Pubitemid 34203054)
30. de Vries MG, Arseneau LM, Lawson ME, Beverly JL. Extracellular glucose in rat ventromedial hypothalamus during acute and recurrent hypoglycemia. Diabetes 2003;52:2767-2773
31. Ainscow EK, Mirshamsi S, Tang T, Ashford ML, Rutter GA. Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(+) channels. J Physiol 2002;544:429-445 (Pubitemid 35244260)
32. Marty N, Dallaporta M, Foretz M, Emery M, Tarussio D, Bady I, Binnert C, Beermann F, Thorens B. Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors (Letter). J Clin Invest 2005; 115:3545-3553 (Pubitemid 43121842)
33. Garcia MA, Millan C, Balmaceda-Aguilera C, Castro T, Pastor P, Montecinos H, Reinicke K, Zuniga F, Vera JC, Onate SA, Nualart F. Hypothalamic ependymal-glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing. J Neurochem 2003;86:709-724 (Pubitemid 36897451)
34. Burdakov D, Luckman SM, Verkhratsky A. Glucose-sensing neurons of the hypothalamus. Philos Trans R Soc Lond B Biol Sci 2005;360:2227-2235
35. Gonzalez JA, Jensen LT, Fugger L, Burdakov D. Metabolism-independent sugar sensing in central orexin neurons. Diabetes 2008;57:2569-2576
36. Chan O, Zhu W, Ding Y, McCrimmon RJ, Sherwin RS. Blockade of GABAA receptors in the ventromedial hypothalamus further stimulates glucagon and sympathoadrenal but not the hypothalamo-pituitary-adrenal response to hypoglycemia. Diabetes 2006; 55:1080-1087 (Pubitemid 44100185)
37. + channels regulate the release of GABA in the ventromedial hypothalamus during hypoglycemia. Diabetes 2007;56:1120-1126
38. Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS. Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia. Diabetes 2008;57: 1363-1370
39. Dunn-Meynell AA, Routh VH, Kang L, Gaspers L, Levin BE. Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons. Diabetes 2002;51:2056-2065 (Pubitemid 34729008)
40. Canabal DD, Song Z, Potian JG, Beuve A, McArdle JJ, Routh VH. Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus. Am J Physiol Regul Integr Comp Physiol 2007;292:R1418-R1428 (Pubitemid 46557799)
41. Hardie DG, Carling D. The AMP-activated protein kinase: fuel gauge of the mammalian cell? Eur J Biochem 1997;246:259-273
42. Mountjoy PD, Bailey SJ, Rutter GA. Inhibition by glucose or leptin of hypothalamic neurons expressing neuropeptide Y requires changes in AMP-activated protein kinase activity. Diabetologia 2007;50: 168-177
43. Fioramonti X, Contie S, Song Z, Routh VH, Lorsignol A, Penicaud L. Characterization of glucosensing neuron subpopulations in the arcuate nucleus: integration in neuropeptide Y and pro-opio melano-cortin networks? Diabetes 2007;56:1219-1227
44. McCrimmon RJ, Fan X, Ding Y, Zhu W, Jacob RJ, Sherwin RS. Potential role for AMP-activated protein kinase in hypoglycemia sensing in the ventromedial hypothalamus. Diabetes 2004;53:1953-1958 (Pubitemid 38970741)
45. McCrimmon RJ, Fan X, Cheng H, McNay E, Chan O, Shaw M, Ding Y, Zhu W, Sherwin RS. Activation of AMP-activated protein kinase within the ventromedial hypothalamus amplifies counterregulatory hormone responses in rats with defective counterregulation. Diabetes 2006; 55:1755-1760 (Pubitemid 44324129)
46. McCrimmon RJ, Shaw M, Fan X, Cheng H, Ding Y, Wang A, Sherwin RS. AMP-activated protein kinase (AMPK): a key mediator of hypoglycemia-sensing in the ventromedial hypothalamus (VMH). Diabetes 2006;55(Suppl.1):A15
47. Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI, Fryer LG, Clements M, Al-Qassab H, Heffron H, Xu AW, Speakman JR, Barsh GS, Viollet B, Vaulont S, Ashford ML, Carling D, Withers DJ. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons (Letter). J Clin Invest 2007;117:2325-2336 (Pubitemid 47219577)
48. Smythe GA, Edwards SR. A role for central postsynaptic alpha 2-adrenoceptors in glucoregulation. Brain Res 1991;562: 225-229
49. Beverly JL, de Vries MG, Beverly MF, Arseneau LM. Norepinephrine mediates glucoprivic-induced increase in GABA in the ventromedial hypothalamus of rats. Am J Physiol Regul Integr Comp Physiol 2000;279:R990-R996
50. Beverly JL, De Vries MG, Bouman SD, Arseneau LM. Noradrenergic and GABAergic systems in the medial hypothalamus are activated during hypoglycemia. Am J Physiol Regul Integr Comp Physiol 2001;280: R563-R569 (Pubitemid 32479702)
51. de Vries MG, Lawson MA, Beverly JL. Hypoglycemia-induced noradrenergic activation in the VMH is a result of decreased ambient glucose. Am J Physiol Regul Integr Comp Physiol 2005;289:R977-R981
52. Ritter S, Dinh TT, Zhang Y. Localization of hindbrain glucoreceptive sites controlling food intake and blood glucose. Brain Res 2000;856:37-47 (Pubitemid 30085509)
53. Song Z, Routh VH. Recurrent hypoglycemia reduces the glucose sensitivity of glucose-inhibited neurons in the ventromedial hypothalamus nucleus. Am J Physiol Regul Integr Comp Physiol 2006;291:R1283-R1287 (Pubitemid 44776701)
54. Choi IY, Seaquist ER, Gruetter R. Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res 2003;72: 25-32 (Pubitemid 36373808)
55. Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS. Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration. Endocrinology 2008;149:1499-1504
56. Bale TL, Vale WW. CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 2004;44:525-527
57. McCrimmon RJ, Song Z, Cheng H, McNay EC, Weikart-Yeckel C, Fan X, Routh VH, Sherwin RS. Corticotrophin-releasing factor receptors within the ventromedial hypothalamus regulate hypoglycemia-induced hormonal counterregulation. J Clin Invest 2006;116:1723-1730 (Pubitemid 43911027)
58. Cheng H, Zhou L, Zhu W, Wang A, Tang C, Chan O, Sherwin RS, McCrimmon RJ. Type 1 corticotrophin-releasing factor receptors in the ventromedial hypothalamus promote hypoglycemia-induced hormonal counterregulation. Am J Physiol 2007 (Pubitemid 47358982)
59. Alquier T, Kawashima J, Tsuji Y, Kahn BB. Role of hypothalamic adenosine 5′-monophosphate-activated protein kinase in the impaired counterregulatory response induced by repetitive neuroglucopenia. Endocrinology 2007;148:1367-1375 (Pubitemid 46272808)