AJP - Endocrinology and Metabolism, Vol 271, Issue 6 E1021-E1028, Copyright © 1996 by American Physiological Society

ARTICLES

Regulation of rat Na+/Pi cotransporter-1 gene expression: the roles of glucose and insulin

H. Li, P. Ren, M. Onwochei, R. J. Ruch and Z. Xie
Department of Pharmacology, Medical College of Ohio, Toledo 43699-0008, USA.

Cytosolic inorganic phosphate (P(i)) 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+/P(i) 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+/P(i) 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+/P(i) 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 P(i) reabsorption in the kidney.

This article has been cited by other articles:

				S. Tiwari, S. Riazi, and C. A. Ecelbarger Insulin's impact on renal sodium transport and blood pressure in health, obesity, and diabetes Am J Physiol Renal Physiol, October 1, 2007; 293(4): F974 - F984. [Abstract] [Full Text] [PDF]

				P. Frei, B. Gao, B. Hagenbuch, A. Mate, J. Biber, H. Murer, P. J. Meier, and B. Stieger Identification and localization of sodium-phosphate cotransporters in hepatocytes and cholangiocytes of rat liver Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G771 - G778. [Abstract] [Full Text] [PDF]

				H. Murer, N. Hernando, I. Forster, and J. Biber Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms Physiol Rev, October 1, 2000; 80(4): 1373 - 1409. [Abstract] [Full Text] [PDF]

				Z. Xie, H. Li, L. Liu, B. B. Kahn, S. M. Najjar, and W. Shah Metabolic regulation of Na+/Pi-cotransporter-1 gene expression in H4IIE cells Am J Physiol Endocrinol Metab, April 1, 2000; 278(4): E648 - E655. [Abstract] [Full Text] [PDF]

				H. Murer, I. Forster, N. Hernando, G. Lambert, M. Traebert, and J. Biber Posttranscriptional regulation of the proximal tubule NaPi-II transporter in response to PTH and dietary Pi Am J Physiol Renal Physiol, November 1, 1999; 277(5): F676 - F684. [Abstract] [Full Text] [PDF]

				H. S. Tenenhouse, S. Roy, J. Martel, and C. Gauthier Differential expression, abundance, and regulation of Na+-phosphate cotransporter genes in murine kidney Am J Physiol Renal Physiol, October 1, 1998; 275(4): F527 - F534. [Abstract] [Full Text] [PDF]

				Y. Taketani, H. Segawa, M. Chikamori, K. Morita, K. Tanaka, S. Kido, H. Yamamoto, Y. Iemori, S. Tatsumi, N. Tsugawa, et al. Regulation of Type II Renal Na+-dependent Inorganic Phosphate Transporters by 1,25-Dihydroxyvitamin D3. IDENTIFICATION OF A VITAMIN D-RESPONSIVE ELEMENT IN THE HUMAN NAPI-3 GENE J. Biol. Chem., June 5, 1998; 273(23): 14575 - 14581. [Abstract] [Full Text] [PDF]

				Y. Soumounou, C. Gauthier, and H. S. Tenenhouse Murine and human type I Na-phosphate cotransporter genes: structure and promoter activity Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1082 - F1091. [Abstract] [Full Text] [PDF]