Relationship between proliferation and glucose metabolism in primary cultures of rabbit proximal tubules

Primary cultures of rabbit proximal tubules, which revert to a glucolytic profile as reflected by increased activity of pyrovate kinase (PK) parallelled by increased glucose consumption and lactate formation, were utilized to explore the relationship between glycolytic metabolism and proliferation. Tubules placed in serum-free, hormonally defined Dulbecco's modified Eagle's medium with 5 mM glucose exhibited logarithmic growth beginning on day 3 in culture. The increase in PK activity lagged ~1 day behind, suggesting that the reversion to glycolysis is a consequence of rather than a prerequisite for cellular proliferation. Tubules cultured in 0.5 mM as contrasted with 25 mM glucose exhibited heightened proliferation reflected by an increase in protein content and cell nunber on day 5 in culture. The heightened proliferation was accompanied by increased PK activity. On day 9, after confluency had been achieved, no differences in protein content or PK activity were detected between tubules cultured in different glucose concentrations. These findings indicate that a low glucose concentration is mitogenic for renal proximal tubules and that the proliferative process in some fashion upregulates the activity of the glycolytic enzyme PK. Furthermore, because accelerated growth proceeds in the presence of glucose restriction, the energy from glycolysis is not required for the proliferative process.