PMID- 16763003
OWN - NLM
STAT- MEDLINE
DCOM- 20061006
LR  - 20181113
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 575
IP  - Pt 1
DP  - 2006 Aug 15
TI  - Differential regulation of metabolic genes in skeletal muscle during starvation 
      and refeeding in humans.
PG  - 291-303
AB  - This study investigated the molecular alterations underlying the physiological 
      adaptations to starvation and refeeding in human skeletal muscle. Forty-eight 
      hours' starvation reduced whole-body insulin sensitivity by 42% and produced 
      marked changes in expression of key carbohydrate (CHO) regulatory genes and 
      proteins: SREBP1c and hexokinase II (HKII) were downregulated 2.5- and 5-fold, 
      respectively, whereas the pyruvate dehydrogenase kinase 4 (PDK4) was upregulated 
      4-fold. These responses were not dependent on the phosphorylation status of Akt 
      and FOXO1. On the other hand, starvation and the concomitant increase in 
      circulating free fatty acids did not upregulate the expression of transcription 
      factors and genes involved in fat metabolism. Twenty-four hours' refeeding with a 
      CHO-rich diet completely reversed the changes in PDK4, HKII and SREBP1c 
      expression in human skeletal muscle but failed to fully restore whole-body 
      insulin sensitivity. Thus, during starvation in healthy humans, unlike rodents, 
      regulation of fat metabolism does not require an adaptive response at 
      transcriptional level, but adaptive changes in gene expression are required to 
      switch off oxidative glucose disposal. Lack of effect on key proteins in the 
      insulin-signalling pathway may indicate that changes in intracellular substrate 
      availability/flux may be responsible for these adaptive changes in glucose 
      metabolism. This may represent an important aspect of the molecular basis of the 
      development of insulin resistance in metabolic conditions characterized by energy 
      restriction.
FAU - Tsintzas, Kostas
AU  - Tsintzas K
AD  - Centre for Integrated Systems Biology and Medicine, School of Biomedical 
      Sciences, University of Nottingham, Nottingham NG7 2UH, UK. 
      kostas.tsintzas@nottingham.ac.uk
FAU - Jewell, Kirsty
AU  - Jewell K
FAU - Kamran, Mo
AU  - Kamran M
FAU - Laithwaite, David
AU  - Laithwaite D
FAU - Boonsong, Tantip
AU  - Boonsong T
FAU - Littlewood, Julie
AU  - Littlewood J
FAU - Macdonald, Ian
AU  - Macdonald I
FAU - Bennett, Andrew
AU  - Bennett A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060608
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Blood Glucose)
RN  - 0 (Dietary Carbohydrates)
RN  - 0 (Insulin)
RN  - 0 (Pyruvate Dehydrogenase Complex)
RN  - 0 (RNA, Messenger)
RN  - 0 (SREBF1 protein, human)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (pyruvate dehydrogenase kinase 4)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adaptation, Physiological
MH  - Adult
MH  - Blood Glucose/metabolism
MH  - Dietary Carbohydrates/administration & dosage
MH  - Eating/*physiology
MH  - *Gene Expression Regulation
MH  - Glucose/*metabolism
MH  - Hexokinase/genetics/metabolism
MH  - Humans
MH  - Insulin/blood
MH  - Insulin Resistance
MH  - Lipid Metabolism
MH  - Male
MH  - Muscle, Skeletal/*enzymology
MH  - Protein Kinases/genetics/metabolism
MH  - Pyruvate Dehydrogenase Complex/metabolism
MH  - RNA, Messenger/metabolism
MH  - Starvation/*enzymology
MH  - Sterol Regulatory Element Binding Protein 1/genetics/metabolism
PMC - PMC1819428
EDAT- 2006/06/10 09:00
MHDA- 2006/10/07 09:00
PMCR- 2007/08/15
CRDT- 2006/06/10 09:00
PHST- 2006/06/10 09:00 [pubmed]
PHST- 2006/10/07 09:00 [medline]
PHST- 2006/06/10 09:00 [entrez]
PHST- 2007/08/15 00:00 [pmc-release]
AID - jphysiol.2006.109892 [pii]
AID - 10.1113/jphysiol.2006.109892 [doi]
PST - ppublish
SO  - J Physiol. 2006 Aug 15;575(Pt 1):291-303. doi: 10.1113/jphysiol.2006.109892. Epub 
      2006 Jun 8.