PMID- 20827264
OWN - NLM
STAT- MEDLINE
DCOM- 20101220
LR  - 20211020
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 30
IP  - 12
DP  - 2010 Dec
TI  - Glycogenolysis in astrocytes supports blood-borne glucose channeling not 
      glycogen-derived lactate shuttling to neurons: evidence from mathematical 
      modeling.
PG  - 1895-904
LID - 10.1038/jcbfm.2010.151 [doi]
AB  - In this article, we examined theoretically the role of human cerebral glycogen in 
      buffering the metabolic requirement of a 360-second brain stimulation, expanding 
      our previous modeling study of neurometabolic coupling. We found that glycogen 
      synthesis and degradation affects the relative amount of glucose taken up by 
      neurons versus astrocytes. Under conditions of 175:115 mmol/L ( approximately 1.5:1) neuronal 
      versus astrocytic activation-induced Na(+) influx ratio,  approximately 12% of astrocytic 
      glycogen is mobilized. This results in the rapid increase of intracellular 
      glucose-6-phosphate level on stimulation and nearly 40% mean decrease of glucose 
      flow through hexokinase (HK) in astrocytes via product inhibition. The 
      suppression of astrocytic glucose phosphorylation, in turn, favors the channeling 
      of glucose from interstitium to nearby activated neurons, without a critical 
      effect on the concurrent intercellular lactate trafficking. Under conditions of 
      increased neuronal versus astrocytic activation-induced Na(+) influx ratio to 
      190:65 mmol/L ( approximately 3:1), glycogen is not significantly degraded and blood glucose is 
      primarily taken up by neurons. These results support a role for astrocytic 
      glycogen in preserving extracellular glucose for neuronal utilization, rather 
      than providing lactate to neurons as is commonly accepted by the current 
      'thinking paradigm'. This might be critical in subcellular domains during 
      functional conditions associated with fast energetic demands.
FAU - DiNuzzo, Mauro
AU  - DiNuzzo M
AD  - Dipartimento di Fisica, Sapienza Universita di Roma, Rome, Italy. 
      mauro.dinuzzo@roma1.infn.it
FAU - Mangia, Silvia
AU  - Mangia S
FAU - Maraviglia, Bruno
AU  - Maraviglia B
FAU - Giove, Federico
AU  - Giove F
LA  - eng
GR  - P41 RR008079/RR/NCRR NIH HHS/United States
PT  - Journal Article
DEP - 20100908
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Blood Glucose)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 9005-79-2 (Glycogen)
SB  - IM
CIN - J Cereb Blood Flow Metab. 2010 Dec;30(12):1982-6. PMID: 20700131
CIN - J Cereb Blood Flow Metab. 2010 Dec;30(12):1893-4. PMID: 20827263
MH  - Astrocytes/*metabolism
MH  - Blood Glucose/*metabolism
MH  - Glycogen/*biosynthesis
MH  - Lactic Acid/metabolism
MH  - Models, Biological
MH  - Neurons/*metabolism
PMC - PMC3002884
EDAT- 2010/09/10 06:00
MHDA- 2010/12/21 06:00
PMCR- 2011/12/01
CRDT- 2010/09/10 06:00
PHST- 2010/09/10 06:00 [entrez]
PHST- 2010/09/10 06:00 [pubmed]
PHST- 2010/12/21 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - jcbfm2010151 [pii]
AID - 10.1038/jcbfm.2010.151 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2010 Dec;30(12):1895-904. doi: 10.1038/jcbfm.2010.151. 
      Epub 2010 Sep 8.