PMID- 9703315
OWN - NLM
STAT- MEDLINE
DCOM- 19980909
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 47
IP  - 8
DP  - 1998 Aug
TI  - Overexpression of glycogen phosphorylase increases GLUT4 expression and glucose 
      transport in cultured skeletal human muscle.
PG  - 1185-92
AB  - Skeletal muscle glucose utilization, a major factor in the control of whole-body 
      glucose tolerance, is modulated in accordance with the muscle metabolic demand. 
      For instance, it is increased in chronic contraction or exercise training in 
      association with elevated expression of GLUT4 and hexokinase II (HK-II). In this 
      work, the contribution of increased metabolic flux to the regulation of the 
      glucose transport capacity was analyzed in cultured human skeletal muscle 
      engineered to overexpress glycogen phosphorylase (GP). Myocytes treated with an 
      adenovirus-bearing muscle GP cDNA (AdCMV-MGP) expressed 10 times higher GP 
      activity and exhibited a twofold increase in the Vmax for 2-deoxy-D-[3H]glucose 
      (2-DG) uptake, with no effect on the apparent Km. The stimulatory effect of 
      insulin on 2-DG uptake was also markedly enhanced in AdCMV-MGP-treated cells, 
      which showed maximal insulin stimulation 2.8 times higher than control cells. No 
      changes in HKII total activity or the intracellular compartmentalization were 
      found. GLUT4, protein, and mRNA were raised in AdCMV-MGP-treated cells, 
      suggesting pretranslational activation. GLUT4 was immunodetected intracellularly 
      with a perinuclear predominance. Culture in glucose-free or high-glucose medium 
      did not alter GLUT4 protein content in either control cells or AdCMV-MGP-treated 
      cells. Control and GP-overexpressing cells showed similar autoinhibition of 
      glucose transport, although they appeared to differ in the mechanism(s) involved 
      in this effect. Whereas GLUT1 protein increased in control cells when they were 
      switched from a high-glucose to a glucose-free medium, GLUT1 remained unaltered 
      in GP-expressing cells upon glucose deprivation. Therefore, the increased 
      intracellular metabolic (glycogenolytic-glycolytic) flux that occurs in muscle 
      cells overexpressing GP causes an increase in GLUT4 expression and enhances basal 
      and insulin-stimulated glucose transport, without significant changes in the 
      autoinhibition of glucose transport. This mechanism of regulation may be 
      operative in the postexercise situation in which GLUT4 expression is upregulated 
      in coordination with increased glycolytic flux and energy demand.
FAU - Baque, S
AU  - Baque S
AD  - Department de Bioquimica i Biologia Molecular, Universitat de Barcelona, Spain.
FAU - Montell, E
AU  - Montell E
FAU - Camps, M
AU  - Camps M
FAU - Guinovart, J J
AU  - Guinovart JJ
FAU - Zorzano, A
AU  - Zorzano A
FAU - Gomez-Foix, A M
AU  - Gomez-Foix AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (SLC2A4 protein, human)
RN  - EC 2.4.1.- (Phosphorylases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Biological Transport/drug effects
MH  - Cells, Cultured
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 4
MH  - Homeostasis/physiology
MH  - Humans
MH  - Insulin/pharmacology
MH  - Monosaccharide Transport Proteins/*metabolism
MH  - *Muscle Proteins
MH  - Muscle, Skeletal/cytology/*metabolism
MH  - Phosphorylases/*metabolism
EDAT- 1998/08/14 00:00
MHDA- 1998/08/14 00:01
CRDT- 1998/08/14 00:00
PHST- 1998/08/14 00:00 [pubmed]
PHST- 1998/08/14 00:01 [medline]
PHST- 1998/08/14 00:00 [entrez]
AID - 10.2337/diab.47.8.1185 [doi]
PST - ppublish
SO  - Diabetes. 1998 Aug;47(8):1185-92. doi: 10.2337/diab.47.8.1185.