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Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells

Drewes, L R
Published in The Journal of clinical investigation. 1999, vol. 104, no. 11, p. 1621-9
Abstract Previous investigations revealed low activities of lactate dehydrogenase (LDH) and plasma membrane monocarboxylate transporters (MCT) in the pancreatic beta cell. In this study the significance of these characteristics was explored by overexpressing type A LDH (LDH-A) and/or type 1 MCT (MCT-1) in the clonal INS-1 beta cells and isolated rat islets. Inducible overexpression of LDH-A resulted in an 87-fold increase in LDH activity in INS-1 cells. Adenovirus-mediated overexpression of MCT-1 increased lactate transport activity 3.7-fold in INS-1 cells. Although overexpression of LDH-A, and/or MCT-1 did not affect glucose-stimulated insulin secretion, LDH-A overexpression resulted in stimulation of insulin secretion even at a low lactate concentration with a concomitant increase in its oxidation in INS-1 cells regardless of MCT-1 co-overexpression. Adenovirus-mediated overexpression of MCT-1 caused an increase in pyruvate oxidation and conferred pyruvate-stimulated insulin release to isolated rat islets. Although lactate did not stimulate insulin secretion from control or MCT-1-overexpressing islets, co-overexpression of LDH-A and MCT-1 evoked lactate-stimulated insulin secretion with a concomitant increase in lactate oxidation in rat islets. These results suggest that low expression of MCT and LDH is requisite to the specificity of glucose in insulin secretion, protecting the organism from undesired hypoglycemic actions of pyruvate and lactate during exercise and other catabolic states.
Keywords Adenoviridae/geneticsAnimalsCarrier Proteins/genetics/metabolismCell LineFluoresceins/metabolismFluorescent Antibody TechniqueGene Expression RegulationGlucose/pharmacologyHydrogen-Ion ConcentrationInsulin/secretionInsulinoma/metabolismIslets of Langerhans/metabolismL-Lactate Dehydrogenase/genetics/metabolismLactic Acid/pharmacologyMonocarboxylic Acid TransportersPyruvic Acid/pharmacologyRatsTransfection
PMID: 10587526
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ISHIHARA, Hisamitsu et al. Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells. In: The Journal of clinical investigation, 1999, vol. 104, n° 11, p. 1621-9. doi: 10.1172/JCI7515 https://archive-ouverte.unige.ch/unige:35092

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Deposited on : 2014-03-28

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