Diabetes affects similarly the catalytic subunit and putative glucose-6-phosphate translocase of glucose-6-phosphatase.
The effect of streptozocin diabetes on the expression of the catalytic subunit (p36) and the putative glucose-6-phosphate translocase (p46) of the glucose-6-phosphatase system (G6Pase) was investigated in rats. In addition to the documented effect of diabetes to increase p36 mRNA and protein in the liver and kidney, a approximately 2-fold increase in the mRNA abundance of p46 was found in liver, kidney, and intestine, and a similar increase was found in the p46 protein level in liver. In HepG2 cells, glucose caused a dose-dependent (1-25 mM) increase (up to 5-fold) in p36 and p46 mRNA and a lesser increase in p46 protein, whereas insulin (1 microM) suppressed p36 mRNA, reduced p46 mRNA level by half, and decreased p46 protein by about 33%. Cyclic AMP (100 microM) increased p36 and p46 mRNA by >2- and 1.5-fold, respectively, but not p46 protein. These data suggest that insulin deficiency and hyperglycemia might each be responsible for up-regulation of G6Pase in diabetes. It is concluded that enhanced hepatic glucose output in insulin-dependent diabetes probably involves dysregulation of both the catalytic subunit and the putative glucose-6-phosphate translocase of the liver G6Pase system.
Li
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Laboratoire d'Endocrinologie Métabolique, Department of Nutrition Groupe de Recherche en Transport Membranaire, Centre de Recherche du CHUM, University of Montreal, Montreal, Quebec H3C 3J7, Canada.
Méchin
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van de Werve
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D000818:Animals; D017920:Antiporters; D020134:Catalytic Domain / Q000235:genetics; D000242:Cyclic AMP / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009004:Monosaccharide Transport Proteins; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D010770:Phosphotransferases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D017920:Antiporters; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C503531:SLC37A4 protein, human; C503533:Slc37a4 protein, rat; C111261:glucose 6-phosphate(transporter); D000242:Cyclic AMP; D010770:Phosphotransferases; D005952:Glucose-6-Phosphatase; D005947:Glucose