PMID- 10480625
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 9
DP  - 1999 Sep
TI  - Conservation of an insulin response unit between mouse and human
      glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR
      binds the insulin response sequence.
PG  - 1885-9
AB  - Because overexpression of the glucose-6-phosphatase catalytic subunit (G-6-Pase) 
      in both type 1 and type 2 diabetes may contribute to the characteristic increased
      rate of hepatic glucose production, we have investigated whether the insulin
      response unit (IRU) identified in the mouse G-6-Pase promoter is conserved in the
      human promoter. A series of human G-6-Pase-chloramphenicol acetyltransferase
      (CAT) fusion genes was transiently transfected into human HepG2 hepatoma cells,
      and the effect of insulin on basal CAT expression was analyzed. The results
      suggest that the IRU identified in the mouse promoter is conserved in the human
      promoter, but that an upstream multimerized insulin response sequence (IRS) motif
      that is only found in the human promoter appears to be functionally inactive. The
      G-6-Pase IRU comprises two distinct promoter regions, designated A and B. Region 
      B contains an IRS, whereas region A acts as an accessory element to enhance the
      effect of insulin, mediated through region B, on basal G-6-Pase gene
      transcription. We have previously shown that the accessory factor binding region 
      A is hepatocyte nuclear factor-1, and we show here that the forkhead protein FKHR
      is a candidate for the insulin-responsive transcription factor binding region B.
FAU - Ayala, J E
AU  - Ayala JE
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University Medical 
      School, Nashville, Tennessee 37232-0615, USA.
FAU - Streeper, R S
AU  - Streeper RS
FAU - Desgrosellier, J S
AU  - Desgrosellier JS
FAU - Durham, S K
AU  - Durham SK
FAU - Suwanichkul, A
AU  - Suwanichkul A
FAU - Svitek, C A
AU  - Svitek CA
FAU - Goldman, J K
AU  - Goldman JK
FAU - Barr, F G
AU  - Barr FG
FAU - Powell, D R
AU  - Powell DR
FAU - O'Brien, R M
AU  - O'Brien RM
LA  - eng
GR  - CA64202/CA/NCI NIH HHS/United States
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - DK38773/DK/NIDDK NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - EC 3.1.3.9 (Glucose-6-Phosphatase)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Catalytic Domain
MH  - Chloramphenicol O-Acetyltransferase/genetics
MH  - Conserved Sequence
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Glucose-6-Phosphatase/chemistry/*genetics
MH  - Humans
MH  - Insulin/*pharmacology
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Promoter Regions, Genetic
MH  - Recombinant Fusion Proteins/drug effects
MH  - *Response Elements
MH  - Transcription Factors/*genetics
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.2337/diabetes.48.9.1885 [doi]
PST - ppublish
SO  - Diabetes. 1999 Sep;48(9):1885-9. doi: 10.2337/diabetes.48.9.1885.