Vanadate reduces sodium-dependent glucose transport and increases glycolytic activity in LLC-PK1 epithelia.
The effect of vanadate pentoxide on apical sodium-dependent glucose transport in LLC-PK1 epithelia was examined. Epithelia grown in the presence or absence of 1 microM vanadate formed confluent monolayers and exhibited no differences in DNA, protein, or ultrastructure. Vanadate-supplemented epithelia demonstrated a lower steady-state alpha-methyl-D-glucopyranoside (AMG) concentrating capacity and a twofold reduction in apical AMG uptake Jmax. This decreased AMG transport occurred as a consequence of a reduction in the number of transport carriers and was not associated with a change in the sodium electrochemical gradient. The vanadate-induced reduction in apical glucose carrier functional activity and expression was accompanied by a stimulation of intracellular glycolytic flux activity, as evidenced by increased glucose consumption, lactate production, PFK-1 activity, and intracellular ATP. There was no difference in intracellular cAMP levels between vanadate-supplemented and non-supplemented epithelia. These results demonstrate an association between stimulation of glycolytic pathway activity and an adaptive response in the form of a reduction in the function and expression of the sodium-dependent apical glucose transporter in LLC-PK1 epithelia.
Madsen
K L
KL
Department of Medicine, University of Alberta, Edmonton, Canada.
Porter
V M
VM
Fedorak
R N
RN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D006601:Hexoses / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D007773:Lactates / Q000378:metabolism; D008757:Methylglucosides / Q000378:metabolism / Q000493:pharmacokinetics; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000502:physiology*; D010695:Phlorhizin / Q000378:metabolism; D012414:Rubidium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism / Q000502:physiology; D013552:Swine; D014638:Vanadates / Q000494:pharmacology*
D006601:Hexoses; D007773:Lactates; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D012414:Rubidium Radioisotopes; D014638:Vanadates; D000255:Adenosine Triphosphate; D010695:Phlorhizin; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose