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Characterization of glucose and SGLT mediated effect on NHE3 in renal proximal tubule
Author(s) -
Pessoa Thaissa Dantas,
Malnic Gerhard
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.689.6
Subject(s) - chemistry , carbohydrate metabolism , glucose transporter , medicine , endocrinology , metabolism , glucose uptake , galactose , perfusion , transporter , biochemistry , biology , insulin , gene
We previously reported that proximal tubule perfusion with glucose 5mM stimulates Na+/H+ exchanger isoform 3 (NHE3) activity via p38MAPKinase pathway. Perfusions with higher glucose concentrations (up to 40 mM) were seen to inhibit NHE3 in comparison to a nominally glucose free solution. However, the role of SGLT1 and/or SGLT2 or glucose metabolism in these distinct effects on NHE3 has not been determined so far. We therefore performed microperfusion experiments with sugar free (CTRL), glucose 5mM (G5) and glucose 40mM (G40) plus 2mM Phloridzin (Plz, a SGLT inhibitor). Plz inhibited CTRL (46,2%) and G5 (60,7%) NHE3 activity but had no additional inhibitory effect on G40 perfusion, showing that SGLT activity is necessary for NHE3 function. In addition, the substitution of glucose by galactose (transported only by SGLT1) completely inhibited the G5 and G40 effect, suggesting that only SGLT2 activity or glucose metabolism modulates NHE3 activity. The substitution of glucose by Methyl α‐D‐glucopyranoside (non‐metabolizable glucose) abolished the G5 but not G40 effect, showing that G5 stimulates NHE3 through glucose metabolism, while G40 did not. We concluded that SGLT activity is necessary for NHE3 function, SGLT2 mediates the effects of both low and high glucose on NHE3 activity and the glucose metabolism is involved with the stimulatory effect of G5 on the transporter. Supported by FAPESP and CNPq