Hyperglycemia-induced changes in Na+/myo-inositol transport, Na(+)-K(+)-ATPase, and protein kinase C activity in proximal tubule cells.
In many tissues, hyperglycemia alters the activities of the Na(+)-dependent myo-inositol (Na/MI) transporter, Na(+)-K(+)-ATPase, and protein kinase C (PKC). However, little is known concerning adaptive changes in renal proximal tubular function after acute or chronic hyperglycemia. We examined hyperglycemia-induced changes in Na/MI transport, Na(+)-K(+)-ATPase activity, and PKC activity using three proximal tubule-like cell lines (JTC12, LLC-PK1, and OK/E cells) and primary cultures of human proximal tubular epithelium (HK cells) cultured for varying periods in low- or high-glucose media, myo-Inositol (MI) transport was mediated by a high-affinity (Km approximately 50 mumol/l) Na(+)-dependent saturable process in the four cell lines. Hyperglycemia produced a time-dependent and persistent increase in Na/MI transport in all cell lines. Chronic hyperglycemia increased the Km for MI transport in LLC-PK1 cells and increased the Vmax in both LLC-PK1 and JTC12 cells. Glucose competitively inhibited Na/MI transport in all low-glucose cells and in high-glucose HK, JTC12, and OK/E cells but had no effect on transport in high-glucose LLC-PK1 cells. Acute hyperglycemia also produced time-dependent increases in Na(+)-K(+)-ATPase activity in all cell lines, a change that persisted only in HK cells. A 24-h exposure to high glucose had no effect on PKC activity in any of the cell lines but increased Ca/phospholipid-dependent PKC activity in membrane fractions from chronically high-glucose LLC-PK1 and OK/E cells. These data suggest that hyperglycemia causes acute changes in proximal tubule function and long-lived adaptive responses in Na/MI transport and the PKC signaling pathway.
Cole
J A
JA
Department of Pharmacology, University of Missouri School of Medicine, Columbia 65212.
Walker
R E
RE
Yordy
M R
MR
D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
D007294:Inositol; D012964:Sodium; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase