Diabetes, Vol 44, Issue 4 446-452, Copyright © 1995 by American Diabetes Association

ARTICLES

Hyperglycemia-induced changes in Na+/myo-inositol transport, Na(+)-K(+)-ATPase, and protein kinase C activity in proximal tubule cells

JA Cole, RE Walker and MR Yordy
Department of Pharmacology, University of Missouri School of Medicine, Columbia 65212.

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.
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