AJP - Cell Physiology, Vol 259, Issue 3 C455-C461, Copyright © 1990 by American Physiological Society
Relationship between proliferation and glucose metabolism in primary cultures of rabbit proximal tubules
M. J. Tang and R. L. Tannen
Division of Nephrology, University of Michigan, Ann Arbor 48109.
Primary cultures of rabbit proximal tubules, which revert to a glycolytic
profile as reflected by increased activity of pyruvate kinase (PK)
paralleled 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
approximately 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 number 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
up-regulates 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.
