Up-regulation of liver glucose-6-phosphatase in x-linked hypophosphatemic mice.
We previously showed that a phosphate-deficient diet resulting in hypophosphatemia upregulated the catalytic subunit p36 of rat liver glucose-6-phosphatase, which is responsible for hepatic glucose production. A possible association between phosphate and glucose homeostasis was now further evaluated in the Hyp mouse, a murine homologue of human X-linked hypophosphatemia. We found that in the Hyp mouse as in the dietary Pi deficiency model, serum insulin was reduced while glycemia was increased, and that liver glucose-6-phosphatase activity was enhanced as a consequence of increased mRNA and protein levels of p36. In contrast, the Hyp model had decreased mRNA and protein levels of the putative glucose-6-phosphate translocase p46 and liver cyclic AMP was not increased as in the phosphate-deficient diet rats. It is concluded that in genetic as in dietary hypophosphatemia, elevated glucose-6-phosphatase activity could be partially responsible for the impaired glucose metabolism albeit through distinct mechanisms.
Xie
W
W
Laboratoire d'Endocrinologie Métabolique, Departments of Nutrition and Biochemistry, Centre de Recherche du CHUM, University of Montreal, Montreal, Canada.
Méchin
M-C
MC
Dubois
S G
SG
Lajeunesse
D
D
van de Werve
G
G
D015720:5'-Nucleotidase; D000818:Animals; D017920:Antiporters; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D015153:Blotting, Western; D000242:Cyclic AMP / Q000032:analysis; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D005952:Glucose-6-Phosphatase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics; D007015:Hypophosphatemia, Familial / Q000201:enzymology* / Q000235:genetics; D007328:Insulin / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000737:chemistry; D009004:Monosaccharide Transport Proteins; D010770:Phosphotransferases / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014960:X Chromosome
D017920:Antiporters; D001786:Blood Glucose; D006023:Glycoproteins; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C503532:Slc37a4 protein, mouse; C503533:Slc37a4 protein, rat; C111261:glucose 6-phosphate(transporter); D000242:Cyclic AMP; D010770:Phosphotransferases; D015720:5'-Nucleotidase; C412794:NT5C3A protein, human; D005952:Glucose-6-Phosphatase