Insulinotropic Action of Methyl Pyruvate: Enzymatic and Metabolic Aspects
| Autor: | Hassan Jijakli, Lynda Cook, Abdellatif Bakkali Nadi, Abdullah Sener, Willy Malaisse, Leonard Best |
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| Rok vydání: | 1996 |
| Předmět: |
Glycerol
Male Pyruvate decarboxylation Pyruvate dehydrogenase kinase Biophysics Pyruvate dehydrogenase phosphatase Biology PKM2 Methylation Biochemistry Rats Sprague-Dawley Islets of Langerhans Insulin Secretion Animals Insulin Dihydrolipoyl transacetylase Pyruvates Molecular Biology L-Lactate Dehydrogenase Methanol Alanine Transaminase Hydrogen-Ion Concentration Pyruvate dehydrogenase complex Mitochondria Rats Pyruvate carboxylase Glucose Gluconeogenesis Extracellular Space |
| Zdroj: | Archives of Biochemistry and Biophysics. 335:245-257 |
| ISSN: | 0003-9861 |
| DOI: | 10.1006/abbi.1996.0505 |
| Popis: | The metabolism of methyl pyruvate was compared to that of pyruvate in isolated rat pancreatic islets. Methyl pyruvate was found to be more efficient than pyruvate in supporting the intramitochondrial conversion of pyruvate metabolites to amino acids, inhibiting D -[5- 3 H]glucose utilization, maintaining a high ratio between D -[3,4- 14 C]glucose or D -[6- 14 C]glucose oxidation and D -[5- 3 H]glucose utilization, inhibiting the intramitochondrial conversion of glucose-derived 2-keto acids to their corresponding amino acids, and augmenting 14 CO 2 output from islets prelabeled with L -[U- 14 C]glutamine. Methyl pyruvate also apparently caused a more marked mitochondrial alkalinization than pyruvate, as judged from comparisons of pH measurements based on the use of either a fluorescein probe or 14 C-labeled 5,5-dimethyl-oxazolidine-2,4-dione. Inversely, pyruvate was more efficient than methyl pyruvate in increasing lactate output and generating L -alanine. These converging findings indicate that, by comparison with exogenous pyruvate, its methyl ester is preferentially metabolized in the mitochondrial, rather than cytosolic, domain of islet cells. It is proposed that both the positive and the negative components of methyl pyruvate insulinotropic action are linked to changes in the net generation of reducing equivalents, ATP and H + . |
| Databáze: | OpenAIRE |
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