Regulation of rat Na+/Pi cotransporter-1 gene expression: the roles of glucose and insulin
Li, H.; Ren, P.; Onwochei, M.; Ruch, R.J.; Xie, Z.
American Journal of Physiology 271(6 Pt 1): E1021-E1028
1996
ISSN/ISBN: 0002-9513 PMID: 8997221 Document Number: 456086
Cytosolic inorganic phosphate (Pi) is important for glucose metabolism. It plays a role in homeostatic regulation of glucose by insulin and glucagon. Recently, we isolated two cDNA clones for rat Na+/Pi cotransporter-1 (rNaPi-1) and demonstrated that they are expressed primarily in the rat liver and kidney. We now report that the expression of rNaPi-1 in these tissues is regulated by fasting and streptozotocin-induced diabetes. Using rat hepatocytes in primary culture, we also demonstrate that glucose and insulin upregulate rNaPi-1 expression, whereas glucagon and elevated intracellular adenosine 3',5'-cyclic monophosphate levels downregulate its expression. Because 2-deoxyglucose exhibits no effect on rNaPi-1 gene expression, we suggest that some metabolite accumulated during glucose metabolism may be responsible for the effects of glucose and insulin on rNaPi-1 gene expression. Our data also reveal that other known Na+/Pi cotransporter genes, NaPi-2 and Ram-1 (a receptor for amphotropic murine retrovirus), are not regulated by insulin and glucose. It is therefore proposed that various subtypes of Na+/Pi cotransporters are differentially regulated and that each subtype may be involved in a specific cellular function. rNaPi-1 may be responsible for Pi uptake by liver and kidney for glucose metabolism, whereas NaPi-2 may play a key role in Pi reabsorption in the kidney. Reprinted by permission of the publisher.