Information de reference pour ce titreAccession Number: | 00003571-200804000-00009.
|
Author: | Herzog, Raimund I.; Chan, Owen; Yu, Sunkyung; Dziura, James; McNay, Ewan C.; Sherwin, Robert S.
|
Institution: | Department of Internal Medicine (R.I.H., O.C., E.C.M., R.S.S.), Section of Endocrinology, and Yale Center for Clinical Investigation (S.Y., J.D.), Yale University School of Medicine, New Haven, Connecticut 06520
|
Title: | |
Source: | Endocrinology. 149(4):1499-1504, April 2008.
|
Abstract: | Our objective was to evaluate whether excessive brain glycogen deposition might follow episodes of acute hypoglycemia (AH) and thus play a role in the hypoglycemia-associated autonomic failure seen in diabetic patients receiving intensive insulin treatment. We determined brain glucose and glycogen recovery kinetics after AH and recurrent hypoglycemia (RH), an established animal model of counterregulatory failure. A single bout of insulin-induced AH or RH for 3 consecutive days was used to deplete brain glucose and glycogen stores in rats. After microwave fixation and glycogen extraction, regional recovery kinetics in the brain was determined using a biochemical assay. Both AH and RH treatments reduced glycogen levels in the cerebellum, cortex, and hypothalamus from control levels of 7.78 +/- 0.55, 5.4 +/- 0.38, and 4.45 +/- 0.37 [mu]mol/g, respectively, to approximately 50% corresponding to a net glycogen utilization rate between 0.6 and 1.2 [mu]mol/g[middle dot]h. After hypoglycemia, glycogen levels returned to baseline within 6 h in both the AH and the RH group. However, recovery of brain glycogen tended to be faster in rats exposed to RH. This effect followed more rapid recovery of brain glucose levels in the RH group, despite similar blood glucose levels in both groups. There was no statistically significant increase above baseline glycogen levels in either group. In particular, brain glycogen was not increased 24 h after the last of recurrent episodes of hypoglycemia, when a significant counterregulatory defect could be documented during a hyperinsulinemic hypoglycemic clamp study. We conclude that glycogen supercompensation is not a major contributory factor to the pathogenesis of hypoglycemia-associated autonomic failure.
Copyright (C) 2008 by The Endocrine Society
|
References: | 1. 1997 Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes 46:271-286
2. 1998 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet [Erratum (1999) 354:602] 352:837-853
3. Cryer PE 2004 Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med 350:2272-2279
4. de Vries MG, Lawson MA, Beverly JL 2005 Hypoglycemia-induced noradrenergic activation in the VMH is a result of decreased ambient glucose. Am J Physiol Regul Integr Comp Physiol 289:R977-R981
5. McCrimmon RJ, Fan X, Ding Y, Zhu W, Jacob RJ, Sherwin RS 2004 Potential role for AMP-activated protein kinase in hypoglycemia sensing in the ventromedial hypothalamus. Diabetes 53:1953-1958
6. Borg MA, Sherwin RS, Borg WP, Tamborlane WV, Shulman GI 1997 Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats. J Clin Invest 99:361-365
7. Wu X, Gao J, Yan J, Owyang C, Li Y 2004 Hypothalamus-brain stem circuitry responsible for vagal efferent signaling to the pancreas evoked by hypoglycemia in rat. J Neurophysiol 91:1734-1747
8. Borg MA, Tamborlane WV, Shulman GI, Sherwin RS 2003 Local lactate perfusion of the ventromedial hypothalamus suppresses hypoglycemic counterregulation. Diabetes 52:663-666
9. Brown AM, Ransom BR 2007 Astrocyte glycogen and brain energy metabolism. Glia 55:1263-1271
10. Brown AM 2004 Brain glycogen re-awakened. J Neurochem 89:537-552
11. Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ 2007 Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251-1262
12. Gruetter R 2003 Glycogen: the forgotten cerebral energy store. J Neurosci Res 74:179-183
13. Passonneau JV, Lauderdale VR 1974 A comparison of three methods of glycogen measurement in tissues. Anal Biochem 60:405-412
14. Sagar SM, Sharp FR, Swanson RA 1987 The regional distribution of glycogen in rat brain fixed by microwave irradiation. Brain Res 417:172-174
15. Swanson RA, Morton MM, Sagar SM, Sharp FR 1992 Sensory stimulation induces local cerebral glycogenolysis: demonstration by autoradiography. Neuroscience 51:451-461
16. Gruetter R 2002 In vivo 13C NMR studies of compartmentalized cerebral carbohydrate metabolism. Neurochem Int 41:143-154
17. Oz G, Henry PG, Seaquist ER, Gruetter R 2003 Direct, noninvasive measurement of brain glycogen metabolism in humans. Neurochem Int 43:323-329
18. Choi IY, Tkac I, Ugurbil K, Gruetter R 1999 Noninvasive measurements of [1-13C]glycogen concentrations and metabolism in rat brain in vivo. J Neurochem 73:1300-1308
19. Choi IY, Seaquist ER, Gruetter R 2003 Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res 72:25-32
20. Choi IY, Lee SP, Kim SG, Gruetter R 2001 In vivo measurements of brain glucose transport using the reversible Michaelis-Menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia. J Cereb Blood Flow Metab 21:653-663
21. Brucklacher RM, Vannucci RC, Vannucci SJ 2002 Hypoxic preconditioning increases brain glycogen and delays energy depletion from hypoxia-ischemia in the immature rat. Dev Neurosci 24:411-417
22. Kong J, Shepel PN, Holden CP, Mackiewicz M, Pack AI, Geiger JD 2002 Brain glycogen decreases with increased periods of wakefulness: implications for homeostatic drive to sleep. J Neurosci 22:5581-5587
23. Cryer PE 2006 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation. Prog Brain Res 153:361-365
24. Agardh CD, Kalimo H, Olsson Y, Siesjo BK 1981 Hypoglycemic brain injury: metabolic and structural findings in rat cerebellar cortex during profound insulin-induced hypoglycemia and in the recovery period following glucose administration. J Cereb Blood Flow Metab 1:71-84
25. Auer RN 2004 Hypoglycemic brain damage. Metab Brain Dis 19:169-175
26. Morgenthaler FD, Koski DM, Kraftsik R, Henry PG, Gruetter R 2006 Biochemical quantification of total brain glycogen concentration in rats under different glycemic states. Neurochem Int 48:616-622
27. Bingham EM, Dunn JT, Smith D, Sutcliffe-Goulden J, Reed LJ, Marsden PK, Amiel SA 2005 Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-d-glucose PET study. Diabetologia 48:2080-2089
28. 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
29. Cruz NF, Dienel GA 2002 High glycogen levels in brains of rats with minimal environmental stimuli: implications for metabolic contributions of working astrocytes. J Cereb Blood Flow Metab 22:1476-1489
30. Sorg O, Magistretti PJ 1992 Vasoactive intestinal peptide and noradrenaline exert long-term control on glycogen levels in astrocytes: blockade by protein synthesis inhibition. J Neurosci 12:4923-4931
31. McCrimmon RJ, Fan X, Cheng H, McNay E, Chan O, Shaw M, Ding Y, Zhu W, Sherwin RS 2006 Activation of AMP-activated protein kinase within the ventromedial hypothalamus amplifies counterregulatory hormone responses in rats with defective counterregulation. Diabetes 55:1755-1760
32. Flanagan DE, Keshavarz T, Evans ML, Flanagan S, Fan X, Jacob RJ, Sherwin RS 2003 Role of corticotrophin-releasing hormone in the impairment of counterregulatory responses to hypoglycemia. Diabetes 52:605-613
33. Hertz L, Peng L, Dienel GA 2006 Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219-249
34. Dienel GA, Cruz NF 2006 Astrocyte activation in working brain: energy supplied by minor substrates. Neurochem Int 48:586-595
35. Franken P, Gip P, Hagiwara G, Ruby NF, Heller HC 2003 Changes in brain glycogen after sleep deprivation vary with genotype. Am J Physiol Regul Integr Comp Physiol 285:R413-R419
36. Franken P, Gip P, Hagiwara G, Ruby NF, Heller HC 2006 Glycogen content in the cerebral cortex increases with sleep loss in C57BL/6J mice. Neurosci Lett 402:176-179
37. Amiel SA, Tamborlane WV, Simonson DC, Sherwin RS 1987 Defective glucose counterregulation after strict glycemic control of insulin-dependent diabetes mellitus. N Engl J Med 316:1376-1383
38. Lei H, Morgenthaler F, Yue T, Gruetter R 2007 Direct validation of in vivo localized 13C MRS measurements of brain glycogen. Magn Reson Med 57:243-248
39. Cranston I, Reed LJ, Marsden PK, Amiel SA 2001 Changes in regional brain 18F-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure. Diabetes 50:2329-2336
40. 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
41. McNay EC, Sherwin RS 2004 Effect of recurrent hypoglycemia on spatial cognition and cognitive metabolism in normal and diabetic rats. Diabetes 53:418-425
42. Boyle PJ, Nagy RJ, O'Connor AM, Kempers SF, Yeo RA, Qualls C 1994 Adaptation in brain glucose uptake following recurrent hypoglycemia. Proc Natl Acad Sci USA 91:9352-9356
43. Cranston I, Marsden P, Matyka K, Evans M, Lomas J, Sonksen P, Maisey M, Amiel SA 1998 Regional differences in cerebral blood flow and glucose utilization in diabetic man: the effect of insulin. J Cereb Blood Flow Metab 18:130-140
44. Ratcheson RA, Blank AC, Ferrendelli JA 1981 Regionally selective metabolic effects of hypoglycemia in brain. J Neurochem 36:1952-1958
45. Cryer PE 1992 Iatrogenic hypoglycemia as a cause of hypoglycemia-associated autonomic failure in IDDM. A vicious cycle. Diabetes 41:255-260
46. Davis MR, Shamoon H 1991 Counterregulatory adaptation to recurrent hypoglycemia in normal humans. J Clin Endocrinol Metab 73:995-1001
47. Brown AM, Sickmann HM, Fosgerau K, Lund TM, Schousboe A, Waagepetersen HS, Ransom BR 2005 Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter. J Neurosci Res 79:74-80
48. Kang L, Dunn-Meynell AA, Routh VH, Gaspers LD, Nagata Y, Nishimura T, Eiki J, Zhang BB, Levin BE 2006 Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes 55:412-420
49. Lam TK, Pocai A, Gutierrez-Juarez R, Obici S, Bryan J, Aguilar-Bryan L, Schwartz GJ, Rossetti L 2005 Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med 11:320-327
50. Alquier T, Kawashima J, Tsuji Y, Kahn BB 2007 Role of hypothalamic adenosine 5'-monophosphate-activated protein kinase in the impaired counterregulatory response induced by repetitive neuroglucopenia. Endocrinology 148:1367-1375
|
Language: | English.
|
Document Type: | Diabetes-Insulin-Glucagon-Gastrointestinal.
|
Journal Subset: | Clinical Medicine.
|
ISSN: | 0013-7227
|
NLM Journal Code: | egz, 0375040
|
Annotation(s) | |
|
|