Glitazones regulate glutamine metabolism by inducing a cellular acidosis in MDCK cells
| Autor: | Greg Coates, Harold D. Battarbee, Itzhak Nissim, Tomas Welbourne |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Physiology Nitrogen Endocrinology Diabetes and Metabolism Intracellular pH Glutamine Biology Kidney Cell Line Rosiglitazone Troglitazone Physiology (medical) Internal medicine Ciglitazone medicine Animals Hypoglycemic Agents Chromans Acidosis L-Lactate Dehydrogenase Nitrogen Isotopes Alanine Transaminase Epithelial Cells Metabolism Hydrogen-Ion Concentration Thiazoles medicine.anatomical_structure Endocrinology Thiazolidinediones medicine.symptom medicine.drug |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 283(4) |
| ISSN: | 0193-1849 |
| Popis: | 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 usingl-[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[Formula: see text]) 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. |
| Databáze: | OpenAIRE |
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