RESUMO
Renal glucose reabsorption is mediated by luminal sodium-glucose cotransporters (SGLTs) and basolateral facilitative glucose transporters (GLUTs). The modulators of these transporters are not known, and their substrates glucose and Na+ are potential candidates. In this study we examined the role of glucose and Na+ filtration rate on gene expression of glucose transporters in renal proximal tubule. SGLT1, SGLT2, GLUT1 and GLUT2 mRNAs were assessed by Northern blotting; and GLUT1 and GLUT2 proteins were assessed by Western blotting. Renal cortex and medulla samples from control rats (C), diabetic rats (D) with glycosuria, and insulin-resistant 15-month old rats (I) without glycosuria; and from normal (NS), low (LS), and high (HS) Na+-diet fed rats were studied. Compared to C and I rats, D rats increased (P < 0.05) gene expression of SGLT2 by approximately 36%, SGLT1 by approximately 20%, and GLUT2 by approximately 100%, and reduced (P < 0.05) gene expression of GLUT1 by more than 50%. Compared to NS rats, HS rats increased (P < 0.05) SGLT2, GLUT2, and GLUT1 expression by approximately 100%, with no change in SGLT1 mRNA expression, and LS rats increased (P < 0.05) GLUT1 gene expression by approximately 150%, with no changes in other transporters. In summary, the results showed that changes in glucose or Na+ filtrated rate modulate the glucose transporters gene expression in epithelial cells of the renal proximal tubule.
Assuntos
Regulação da Expressão Gênica , Glucose/metabolismo , Túbulos Renais Proximais/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Sódio/metabolismo , Animais , Northern Blotting , Western Blotting , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Dieta , Taxa de Filtração Glomerular , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 2 , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , RNA Mensageiro , Ratos , Ratos Wistar , Transportador 1 de Glucose-Sódio , Transportador 2 de Glucose-SódioRESUMO
The mechanism of proximal tubule potassium reabsorption was studied by stopped-flow microperfusion and determination of potassium activities by ion-sensitive resin microelectrodes. The proximal tubule was unable to establish transepithelial potassium gradients. Perfusion with 20 mM K+ turned the lumen 3 mV more negative, an effect abolished by Ba2+. The half-time for K+ activities to reach their stationary level after perfusion with 1 mM K+ was significantly increased by Ba2+ from 4.25 +/- 0.14 s to 11.0 +/- 1.71 s, and after perfusion with 20 mM K+, from 5.43 +/- 0.20 to 12.53 +/- 0.90 s. These data indicate that a significant fraction of potassium is transferred across proximal tubule epithelium by a transcellular, K(+)-channel-dependent route.
Assuntos
Túbulos Renais Proximais/metabolismo , Potássio/farmacocinética , Animais , Bário/farmacologia , Transporte Biológico , Epitélio/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Perfusão , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/fisiologia , Ratos , Ratos EndogâmicosRESUMO
The mechanism of proximal tubule potassium reabsorption was studied by stopped-flow microperfusion and determination of potassium activities by ion-sensitive resin microelectrodes. The proximal tubule was unable to establish transepithelial potassium gradients. perfusion with 20 mM K+ turned the lumen 3 mV more negative, an effect abolished by Ba2+. the half-time for K+ activities to reach their stationary level after perfusion with 1 mMK+ was significantly increased by Ba2+ from 4.25 ñ 0.14sto 11.0 ñ 1.71s, and aftr perfusion with 20 mMK+, from 5.43 ñ 0.20 to 12.53 ñ 0.90s. These data indicate that a significant fraction of potassium is transferred across proximal tubule spithelium by a transcellular, K+-channel-dependent route