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 ∼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.
Hyperglycemia-Induced Changes in Na+/myo-Inositol Transport, Na+-K+-ATPase, and Protein Kinase C Activity in Proximal Tubule Cells
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Judith A Cole, Ruth E W Walker, Michael R Yordy; Hyperglycemia-Induced Changes in Na+/myo-Inositol Transport, Na+-K+-ATPase, and Protein Kinase C Activity in Proximal Tubule Cells. Diabetes 1 April 1995; 44 (4): 446–452. https://doi.org/10.2337/diab.44.4.446
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