Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 283, Issue 4, Pages E729-E737Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00485.2001
Keywords
rosiglitazone; troglitazone; ciglitazone; L-[2-N-15] glutamine; 2 ',7 '-bis(2-carboxyethyl)-5(6)-carboxyfluorescein; glutamate; alanine; ammonium; Madin-Darby canine kidney cells; intracellular pH
Categories
Funding
- NIDDK NIH HHS [DK-53761] Funding Source: Medline
Ask authors/readers for more resources
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 muM) 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-N-15]glutamine and measuring the [N-15]alanine and [N-15]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 (NH4+) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available