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GLUT2 protein at the rat proximal tubule brush border membrane correlates with protein kinase C (PKC)-beta 1 and plasma glucose concentration

Goestemeyer, AK; Marks, J; Srai, SK; Debnam, ES; Unwin, RJ; (2007) GLUT2 protein at the rat proximal tubule brush border membrane correlates with protein kinase C (PKC)-beta 1 and plasma glucose concentration. DIABETOLOGIA , 50 (10) 2209 - 2217. 10.1007/s00125-007-0778-x.

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Abstract

Aims/hypothesis GLUT2 is the main renal glucose transporter upregulated by hyperglycaemia, when it becomes detectable at the brush border membrane (BBM). Since glucose-induced protein kinase C (PKC) activation in the kidney is linked to diabetic nephropathy, we investigated the effect of glycaemic status on the protein levels of PKC isoforms alpha, beta I, beta II, delta and epsilon in the proximal tubule, as well as the relationship between them and changes in GLUT2 production at the BBM.Methods Plasma glucose concentrations were modulated in rats by treatment with nicotinamide 15 min prior to induction of diabetes with streptozotocin. Levels of GLUT2 protein and PKC isoforms in BBM were measured by western blotting. Additionally, the role of calcium signalling and PKC activation on facilitative glucose transport was examined by measuring glucose uptake in BBM vesicles prepared from proximal tubules that had been incubated either with thapsigargin, which increases cytosolic calcium, or with the PKC activator phorbol 12-myristate,13-acetate (PMA).Results Thapsigargin and PMA enhanced GLUT-mediated glucose uptake, but had no effect on sodium-dependent glucose transport. Diabetes significantly increased the protein levels of GLUT2 and PKC-beta I at the BBM. Levels of GLUT2 and PKC-beta I correlated positively with plasma glucose concentration. Diabetes had no effect on BBM levels of alpha, beta II, delta or epsilon isoforms of PKC.Conclusion/interpretation Enhanced GLUT2-mediated glucose transport across the proximal tubule BBM during diabetic hyperglycaemia is closely associated with increased PKC-beta I. Thus, altered levels of GLUT2 and PKC-beta I proteins in the BBM may be important factors in the pathogenic processes underlying diabetic renal injury.

Type: Article
Title: GLUT2 protein at the rat proximal tubule brush border membrane correlates with protein kinase C (PKC)-beta 1 and plasma glucose concentration
DOI: 10.1007/s00125-007-0778-x
Keywords: brush border membrane, diabetes, facilitated glucose transporters, GLUT2, hyperglycaemia, protein kinase C, proximal tubule, streptozotocin, INDUCED DIABETIC-RATS, PKC-BETA INHIBITOR, EXTRACELLULAR-MATRIX, INTESTINAL GLUCOSE, CALCIUM-ABSORPTION, GENE-EXPRESSION, DECREASED DEGRADATION, OXIDATIVE STRESS, SUGAR-TRANSPORT, MESSENGER-RNA
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/8593
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