PMID- 10604279
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20111117
IS  - 1078-0297 (Print)
IS  - 1078-0297 (Linking)
VI  - 104
IP  - 1
DP  - 1999
TI  - Insulin stimulation of glutamine: fructose-6-phosphate amidotransferase occurs
      via an insulin-like growth factor-1 pathway in rat fibroblasts.
PG  - 63-72
AB  - The biosynthetic pathway for hexosamine mediates some of the adverse effects of
      high glucose. The rate limiting enzyme in this pathway is
      glutamine:fructose-6-phosphate amidotransferase (GFA). Using HPLC, the regulation
      of GFA activity by glucose and insulin was studied in wild type and rat-1
      fibroblasts overexpressing human insulin receptors (HIRcB cells). In wild type
      cells only maximal doses of insulin (580 ng/ml) resulted in an increase in GFA
      activity (51.0 +/- 40.6%). In HIRcB cells insulin led to a dose dependent
      increase in GFA activity that was enhanced when compared to wild type (89 +/- 5% 
      (p<0.001) increase at 580 ng/ml). Insulin's action was glucose dependent and
      required prolonged serum deprivation. HIRcB's cultured in 0 mM glucose had a
      58.2% (p<0.001) decrease in insulin stimulation. However, when present the
      concentration of glucose (2-20 mM) did not affect insulin stimulation of GFA
      activity. Most of insulin's effects occur by way of the IGF-1 receptor as a
      two-fold stimulation of GFA activity was seen with significantly lower doses (10 
      ng/ml) of IGF-1. We conclude that GFA enzyme activity is upregulated by insulin
      and this may occur via a IGF-1 receptor mediated pathway.
FAU - Simmons, S T
AU  - Simmons ST
AD  - Department of Medicine, University of Mississippi Medical Center, Jackson 39216, 
      USA.
FAU - Daniels, M C
AU  - Daniels MC
FAU - Huddleston, E
AU  - Huddleston E
FAU - Hebert, L F Jr
AU  - Hebert LF Jr
FAU - McClain, D A
AU  - McClain DA
FAU - Crook, E D
AU  - Crook ED
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Res Commun Mol Pathol Pharmacol
JT  - Research communications in molecular pathology and pharmacology
JID - 9437512
RN  - 0 (Insulin)
RN  - 0 (Receptors, Somatomedin)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.6.1.16 (Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing))
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Enzyme Activation
MH  - Fibroblasts/drug effects/enzymology/metabolism
MH  - Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/*metabolism
MH  - Insulin/*pharmacology
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Rats
MH  - Receptors, Somatomedin/metabolism
EDAT- 1999/12/22 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/12/22 09:00
PHST- 1999/12/22 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/12/22 09:00 [entrez]
PST - ppublish
SO  - Res Commun Mol Pathol Pharmacol. 1999;104(1):63-72.