The inhibition of gluconeogenesis by chloroquine contributes to its hypoglycaemic action
Identifieur interne : 002258 ( Main/Exploration ); précédent : 002257; suivant : 002259The inhibition of gluconeogenesis by chloroquine contributes to its hypoglycaemic action
Auteurs : Robert Jarzyna [Pologne] ; Anna Kiersztan [Pologne] ; Olesia Lisowa [Pologne] ; Jadwiga Bryła [Pologne]Source :
- European Journal of Pharmacology [ 0014-2999 ] ; 2001.
English descriptors
- Teeft :
- Alanine, Amino, Amino acids, Antihyperglycaemic action, Bicarbonate buffer, Biochem, Carboxykinase, Chloroquine, Clin, Dehydrogenase, Diabetes mellitus, Diabetic animals, European journal, Gerich, Gluconeogenesis, Gluconeogenic, Gluconeogenic intermediates, Glucose, Glucose formation, Glucose production, Glucose synthesis, Glutamate, Glutamate dehydrogenase, Glutamate dehydrogenase activity, Glutamateq glycerolq octanoate, Glutamine, Glycerol, Healthy volunteers, Hepatocytes, Hypoglycaemic, Hypoglycaemic action, Incubation medium, Inhibitory action, Inhibitory effect, Insulin, Insulin receptor, Intracellular, Intracellular content, Jarzyna, Kidney tubules, Lactate, Malate, Mellitus, Metabolism, Mgy1, Mitochondrion, Nmol, Nmol miny1 mgy1, Octanoate, Other substrates, Oxygen consumption, Pharmacology, Phosphoenolpyruvate, Phosphoenolpyruvate carboxykinase, Phosphoenolpyruvate carboxykinase activity, Pyruvate, Rabbit tubules, Renal, Renal gluconeogenesis, Renal tubules, Separate experiments, Stumvoll, Tubule, Urea production.
Abstract
Abstract: The effect of chloroquine on gluconeogenesis in isolated hepatocytes and kidney-cortex tubules of rabbit has been studied. The inhibitory action of 200 μM chloroquine was the highest in hepatocytes and renal tubules incubated with glutamine and glutamate+glycerol+octanoate, respectively, while in the presence of other substrates the drug action was less pronounced. With amino acids as substrates, the inhibition of gluconeogenesis was accompanied by a decreased glutamine production, resulting from a decline of glutamate dehydrogenase activity. A decrease in the urea production by hepatocytes incubated with chloroquine in the presence of glutamine but not NH4Cl as the source of ammonium is in agreement with this suggestion. The degree of inhibition by chloroquine of the rate of gluconeogenesis in renal tubules isolated from control rabbits was similar to that determined in diabetic animals. Chloroquine-induced changes in levels of intracellular gluconeogenic intermediates indicate a decrease in phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities probably due to increased concentration of 2-oxoglutarate, an inhibitor of these two enzymes. In view of the data, it is likely that inhibition by chloroquine of glucose formation in liver and kidney may contribute to the hypoglycaemic action of this drug. The importance of the inhibitory effect of chloroquine on glutamate dehydrogenase activity in the antihyperglycaemic action of the drug is discussed.
Url:
DOI: 10.1016/S0014-2999(01)01221-3
Affiliations:
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Le document en format XML
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<term>Bicarbonate buffer</term>
<term>Biochem</term>
<term>Carboxykinase</term>
<term>Chloroquine</term>
<term>Clin</term>
<term>Dehydrogenase</term>
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<term>Hypoglycaemic</term>
<term>Hypoglycaemic action</term>
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<term>Nmol miny1 mgy1</term>
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<term>Pharmacology</term>
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<term>Phosphoenolpyruvate carboxykinase activity</term>
<term>Pyruvate</term>
<term>Rabbit tubules</term>
<term>Renal</term>
<term>Renal gluconeogenesis</term>
<term>Renal tubules</term>
<term>Separate experiments</term>
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<front><div type="abstract" xml:lang="en">Abstract: The effect of chloroquine on gluconeogenesis in isolated hepatocytes and kidney-cortex tubules of rabbit has been studied. The inhibitory action of 200 μM chloroquine was the highest in hepatocytes and renal tubules incubated with glutamine and glutamate+glycerol+octanoate, respectively, while in the presence of other substrates the drug action was less pronounced. With amino acids as substrates, the inhibition of gluconeogenesis was accompanied by a decreased glutamine production, resulting from a decline of glutamate dehydrogenase activity. A decrease in the urea production by hepatocytes incubated with chloroquine in the presence of glutamine but not NH4Cl as the source of ammonium is in agreement with this suggestion. The degree of inhibition by chloroquine of the rate of gluconeogenesis in renal tubules isolated from control rabbits was similar to that determined in diabetic animals. Chloroquine-induced changes in levels of intracellular gluconeogenic intermediates indicate a decrease in phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities probably due to increased concentration of 2-oxoglutarate, an inhibitor of these two enzymes. In view of the data, it is likely that inhibition by chloroquine of glucose formation in liver and kidney may contribute to the hypoglycaemic action of this drug. The importance of the inhibitory effect of chloroquine on glutamate dehydrogenase activity in the antihyperglycaemic action of the drug is discussed.</div>
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