Selective stimulation of G-6-Pase catalytic subunit but not G-6-P transporter gene expression by glucagon in vivo and cAMP in situ.
We recently compared the regulation of glucose-6-phosphatase (G-6-Pase) catalytic subunit and glucose 6-phosphate (G-6-P) transporter gene expression by insulin in conscious dogs in vivo (Hornbuckle LA, Edgerton DS, Ayala JE, Svitek CA, Neal DW, Cardin S, Cherrington AD, and O'Brien RM. Am J Physiol Endocrinol Metab 281: E713-E725, 2001). In pancreatic-clamped, euglycemic conscious dogs, a 5-h period of hypoinsulinemia led to a marked increase in hepatic G-6-Pase catalytic subunit mRNA; however, G-6-P transporter mRNA was unchanged. Here, we demonstrate, again using pancreatic-clamped, conscious dogs, that glucagon is a candidate for the factor responsible for this selective induction. Thus glucagon stimulated G-6-Pase catalytic subunit but not G-6-P transporter gene expression in vivo. Furthermore, cAMP stimulated endogenous G-6-Pase catalytic subunit gene expression in HepG2 cells but had no effect on G-6-P transporter gene expression. The cAMP response element (CRE) that mediates this induction was identified through transient transfection of HepG2 cells with G-6-Pase catalytic subunit-chloramphenicol acetyltransferase fusion genes. Gel retardation assays demonstrate that this CRE binds several transcription factors including CRE-binding protein and CCAAT enhancer-binding protein.
Hornbuckle
Lauri A
LA
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0615, USA.
Everett
Carrie A
CA
Martin
Cyrus C
CC
Gustavson
Stephanie S
SS
Svitek
Christina A
CA
Oeser
James K
JK
Neal
Doss W
DW
Cherrington
Alan D
AD
O'Brien
Richard M
RM
D000818:Animals; D017920:Antiporters; D020134:Catalytic Domain / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D005934:Glucagon / Q000502:physiology*; D015309:Glucose Clamp Technique; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D015290:Second Messenger Systems / Q000502:physiology
D017920:Antiporters; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C111261:glucose 6-phosphate(transporter); D005934:Glucagon; D000242:Cyclic AMP; D010770:Phosphotransferases; D005952:Glucose-6-Phosphatase; D005990:Glycerol