LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic ß cells.
Cell Rep
; 43(4): 114047, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38607916
ABSTRACT
Using 13C6 glucose labeling coupled to gas chromatography-mass spectrometry and 2D 1H-13C heteronuclear single quantum coherence NMR spectroscopy, we have obtained a comparative high-resolution map of glucose fate underpinning ß cell function. In both mouse and human islets, the contribution of glucose to the tricarboxylic acid (TCA) cycle is similar. Pyruvate fueling of the TCA cycle is primarily mediated by the activity of pyruvate dehydrogenase, with lower flux through pyruvate carboxylase. While the conversion of pyruvate to lactate by lactate dehydrogenase (LDH) can be detected in islets of both species, lactate accumulation is 6-fold higher in human islets. Human islets express LDH, with low-moderate LDHA expression and ß cell-specific LDHB expression. LDHB inhibition amplifies LDHA-dependent lactate generation in mouse and human ß cells and increases basal insulin release. Lastly, cis-instrument Mendelian randomization shows that low LDHB expression levels correlate with elevated fasting insulin in humans. Thus, LDHB limits lactate generation in ß cells to maintain appropriate insulin release.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Láctico
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Células Secretoras de Insulina
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Secreção de Insulina
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L-Lactato Desidrogenase
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article