Transcriptomics

Dataset Information

0

Redox state and altered pyruvate metabolism contribute to a dose-dependent metformin-induced lactate production of human myotubes


ABSTRACT: Metformin-induced lactate production can lead to lactate acidosis as life-threatening side effect, whereas lactate in a physiological range might also be involved in the therapeutic effect. How metformin increases systemic lactate concentrations is only partly understood. Since human skeletal muscle has a high capacity to produce lactate, we aim to elucidate the potential contribution of skeletal muscle and the dose-dependent regulation of metformin-induced lactate production in primary human myotubes after 48 h of metformin treatment (16-776 μM). At 78 µM, metformin induced lactate production and glucose consumption. Investigating the cellular redox state by mitochondrial respirometry, we found metformin to inhibit the respiratory chain complex I (776 µM, p<0.01) along with a decreased [NAD+]:[NADH] ratio (776 µM, p<0.001). RNA sequencing and phospho-immunoblot data indicate inhibition of pyruvate oxidation mediated through phosphorylation of PDH complex (39 µM, p<0.01). In vivo in human skeletal muscle, we found pyruvate metabolism altered by exercise and not by metformin. Nonetheless, blood lactate levels in the pre-exercise condition are increased under metformin treatment (p<0.05). Metformin-induced inhibition of pyruvate oxidation combined with altered cellular redox state, both shift the equilibrium of the LDH reaction leading to enhanced lactate production of human myotubes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229658 | GEO | 2023/09/04

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2011-12-12 | E-GEOD-29055 | biostudies-arrayexpress
2023-04-19 | GSE221941 | GEO
2024-09-25 | GSE272113 | GEO
2011-12-12 | GSE29055 | GEO
2005-08-11 | GSE3078 | GEO
2012-01-01 | GSE30192 | GEO
2010-06-23 | E-GEOD-18589 | biostudies-arrayexpress
2012-01-01 | E-GEOD-30192 | biostudies-arrayexpress
2010-04-25 | E-GEOD-21287 | biostudies-arrayexpress
2021-11-11 | PXD029693 |