AJP - Renal Physiology, Vol 249, Issue 2 256-F262, Copyright © 1985 by American Physiological Society
Phorbol esters inhibit gluconeogenesis in canine renal proximal tubular segments
S. Rogers, J. R. Gavin 3rd and M. R. Hammerman
Gluconeogenesis is a major metabolic function of the renal proximal tubular
cell. To characterize the regulation of this process in proximal tubule,
glucose production from gluconeogenic precursors was measured in proximal
tubular segments prepared from dog kidney. Production of glucose was a
linear function of time for up to 120 min of incubation at 37 degrees C
under a variety of conditions. Lowering the pH of incubation media from 7.5
to 7.0 increased glucose synthesis. Production of glucose was inhibited by
3-mercaptopicolinate. Incubation of proximal tubular segments with insulin
diminished synthesis of glucose. Incubation of segments with
tumor-promoting phorbol esters, 12-O-tetradecanoylphorbol-13-acetate or
phorbol 12,13-dibutyrate, resulted in decreased production of glucose. This
effect was not observed following incubation with the inactive phorbol
ester 4 alpha-phorbol. Changes in glucose synthesis could not be attributed
to alterations in cell viability or in rates of glucose oxidation induced
by experimental maneuvers. Our findings confirm the usefulness of proximal
tubular segments for characterization of metabolic processes in this
portion of the nephron. The experimental results are consistent with a role
for protein kinase C in the control of gluconeogenesis in proximal tubule.
