REGULATION OF RAT NA+ P-I COTRANSPORTER-1 GENE-EXPRESSION - THE ROLESOF GLUCOSE AND INSULIN/

Cytosolic inorganic phosphate (P-i) is important for glucose metabolis m. It plays a role in homeostatic regulation of glucose by insulin and glucagon. Recently, we isolated two cDNA clones for rat Na+/P-i cotra nsporter-1 (rNaPi-1) and demonstrated that they are expressed primaril y in the rat liver and kidney. We now report that the expression of rN aPi-1 in these tissues is regulated by fasting and streptozotocin-indu ced diabetes. Using rat hepatocytes in primary culture, we also demons trate that glucose and insulin upregulate rNaPi-1 expression, whereas glucagon and elevated intracellular adenosine 3',5'-cyclic monophospha te 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 effe cts of glucose and insulin on rNaPi-1 gene expression. Our data also r eveal that other known Na+/P-i cotransporter genes, NaPi-2 and Ram-1 ( a receptor for amphotropic murine retrovirus), are not regulated by in sulin and glucose. It is therefore proposed that various subtypes of N a+/P-i cotransporters are differentially regulated and that each subty pe may be involved in a specific cellular function. rNaPi-1 may be res ponsible for P-i uptake by liver and kidney for glucose metabolism, wh ereas NaPi-2 may play a key role in P-i reabsorption in the kidney.