Differential regulation of three glucose transporter genes in a renal epithelial cell line

Abstract

Three hexose transporter genes, the Na(+)/glucose cotransporters SGLT1 and SGLT3 (formerly SAAT1/pSGLT2) and the facilitative transporter GLUT1, are expressed in a renal epithelial cell line with proximal tubule characteristics. A number of studies have demonstrated that SGLT1 expression is coupled to the cellular differentiation state and is also negatively regulated by its substrate glucose. In the present study, we demonstrate that SGLT3 mRNA expression is relatively unaffected by conditions promoting dedifferentiation (reseeding to a subconfluent density, activation of protein kinase C) or differentiation (confluent cell density, activation of protein kinase A) nor was expression sensitive to hyperglycemic glucose levels in the medium. We further demonstrate that protein kinase A and protein kinase C exert opposing effects on GLUT1 and SGLT1 mRNA levels in polarized cell monolayers, indicating that GLUT1 mRNA is also highly regulated in polarized epithelial cells by agents affecting cell differentiation. The relatively constitutive expression of SGLT3 mRNA suggests a novel role for this low-affinity Na(+)/glucose cotransporter, to provide concentrative glucose uptake under hyperglycemic conditions where expression of high-affinity glucose cotransporter SGLT1 mRNA is significantly downregulated.

Effect of EGF on H2O2‐induced inhibition of α‐MG uptake in renal proximal tubule cells: Involvement of MAPK and AA release

“…Indeed the observed inhibition of α‐MG uptake caused by a combination of EGF and H 2 O 2 was completely reversed by PD 98059 and mepacrine. Thus, our results indicate the involvement of the p44/42 MAPK pathway, which lies at the heart of many signal transduction processes and constitutes a major pathway through which growth factors transduce signals to the nucleus following their interaction with specific receptors (Chakraborti and Chakraborti, 1998; Clancey and Lever, 2000; Kolch, 2000).…”

“…Apically localized Na + /glucose cotransporters in the renal proximal tubule play a central role in the reabsorption of glucose from the glomerular filtrate by mediating the transport of glucose into renal proximal tubule cells (PTCs). Subsequently, efflux of accumulated intracellular glucose occurs by means of facilitated diffusion systems for glucose localized in the basolateral membrane (Clancey and Lever, 2000; Wright, 2001). During instances of where filtered glucose is incompletely reabsorbed, a consequence is osmotic effects, which disrupt normal fluid and electrolyte homeostasis, as exemplified in poorly controlled diabetic mellitus (Oku et al, 2000).…”

Evaluation of Proliferation and Functional Differentiation of LLC-PK1 Cells on Porous Polymer Membranes for the Development of a Bioartificial Renal Tubule Device

“…18,19 SGLT1 is an apical site transporter and its mRNA expression is observed just after confluence is reached. 18,19 SGLT1 expression is associated with cellular differentiation. 19 In the present study, we demonstrated that SGLT1 mRNA expression was maintained for 3 weeks after the cells reached confluency, regardless of overconfluency (Fig.…”

“…GLUT1 mRNA is expressed during the growth and differentiation phases. 18,19 SGLT1 is an apical site transporter and its mRNA expression is observed just after confluence is reached. 18,19 SGLT1 expression is associated with cellular differentiation.…”

“…18,19 SGLT1 expression is associated with cellular differentiation. 19 In the present study, we demonstrated that SGLT1 mRNA expression was maintained for 3 weeks after the cells reached confluency, regardless of overconfluency (Fig. 6).…”