AJP - Endo Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 283: E729-E737, 2002. First published April 2, 2002; doi:10.1152/ajpendo.00485.2001
0193-1849/02 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
283/4/E729    most recent
00485.2001v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Coates, G.
Right arrow Articles by Welbourne, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coates, G.
Right arrow Articles by Welbourne, T.
Vol. 283, Issue 4, E729-E737, October 2002

Glitazones regulate glutamine metabolism by inducing a cellular acidosis in MDCK cells

Greg Coates1, Itzhak Nissim2, Harold Battarbee1, and Tomas Welbourne1

1 Departments of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, Louisiana 71130; and 2 Division of Child Development and Rehabilitation, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

We studied the effect of the antihyperglycemic glitazones, ciglitazone, troglitazone, and rosiglitazone, on glutamine metabolism in renal tubule-derived Madin-Darby canine kidney (MDCK) cells. Troglitazone (25 µM) enhanced glucose uptake and lactate production by 108 and 92% (both P < 0.001). Glutamine utilization was not inhibited, but alanine formation decreased and ammonium formation increased (both P < 0.005). The decrease in net alanine formation occurred with a change in alanine aminotransferase (ALT) reactants, from close to equilibrium to away from equilibrium, consistent with inhibition of ALT activity. A shift of glutamine's amino nitrogen from alanine into ammonium was confirmed by using L-[2-15N]glutamine and measuring the [15N]alanine and [15N]ammonium production. The glitazone-induced shift from alanine to ammonium in glutamate metabolism was dose dependent, with troglitazone being twofold more potent than rosiglitazone and ciglitazone. All three glitazones induced a spontaneous cellular acidosis, reflecting impaired acid extrusion in responding to both an exogenous (NH<UP><SUB>4</SUB><SUP>+</SUP></UP>) and an endogenous (lactic acid) load. Our findings are consistent with glitazones inducing a spontaneous cellular acidosis associated with a shift in glutamine amino nitrogen metabolism from predominantly anabolic into a catabolic pathway.

rosiglitazone; troglitazone; ciglitazone; L-[2-15N]glutamine; 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein; glutamate; alanine; ammonium; Madin-Darby canine kidney cells; intracellular pH


This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
F. Turturro, R. Oliver III, E. Friday, I. Nissim, and T. Welbourne
Troglitazone and pioglitazone interactions via PPAR-{gamma}-independent and -dependent pathways in regulating physiological responses in renal tubule-derived cell lines
Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1137 - C1146.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
R. Oliver III, E. Friday, F. Turturro, A. Lacy, and T. Welbourne
Troglitazone's rapid and sustained activation of ERK1/2 induces cellular acidosis in LLC-PK1-F+ cells: physiological responses
Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1257 - F1266.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W. Nie, S. Sweetser, M. Rinella, and R. M. Green
Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator agonist receptor-{alpha} and -{gamma}
Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G207 - G212.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
T. Welbourne, E. Friday, R. Fowler, F. Turturro, and I. Nissim
Troglitazone acts by PPAR{gamma} and PPAR{gamma}-independent pathways on LLC-PK1-F+ acid-base metabolism
Am J Physiol Renal Physiol, January 1, 2004; 286(1): F100 - F110.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online