Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetes
Changes in cellular bioenergetics such as mitochondrial respiration and glycolysis may play a role in the pathogenesis of various diseases including type 1 diabetes (T1D). We used Seahorse extracellular flux technology to analyse the efficiency of glycolysis and mitochondrial oxidative phosphorylati...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022035927 |
| _version_ | 1828071280165781504 |
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| author | Joana Mendes Lopes de Melo Jens Christian Laursen Niels Søndergaard-Heinrich Ida Kirstine Bull Rasmussen Christian Stevns Hansen Marie Frimodt-Møller Peter Rossing Joachim Størling |
| author_facet | Joana Mendes Lopes de Melo Jens Christian Laursen Niels Søndergaard-Heinrich Ida Kirstine Bull Rasmussen Christian Stevns Hansen Marie Frimodt-Møller Peter Rossing Joachim Størling |
| author_sort | Joana Mendes Lopes de Melo |
| collection | DOAJ |
| description | Changes in cellular bioenergetics such as mitochondrial respiration and glycolysis may play a role in the pathogenesis of various diseases including type 1 diabetes (T1D). We used Seahorse extracellular flux technology to analyse the efficiency of glycolysis and mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells (PBMCs) obtained from fresh blood samples from fifteen long-term T1D individuals with albuminuria (five females) with an average (±SD) age of 58 (±14) years and 15 age and sex-matched healthy non-diabetic controls. In T1D PBMCs, mitochondrial proton leak was higher (T1D: 21,3 ± 1,46 pmol/min; controls: 17,3 ± 1,24 pmol/min; p = 0,049) and glucose (5 mM) suppressed mitochondrial proton leak more than in healthy controls. Further, PBMCs from T1D individuals had higher glycolysis compared with healthy controls (T1D: 9,68 ± 0,94 mpH/min; controls: 7,07 ± 0,64 mpH/min; p = 0,032). Correlation analysis of circulating inflammatory factors identified Leukaemia Inhibitor factor 1 (LIF) being negatively correlated with PBMC glycolysis. Our results suggest that mitochondrial and glycolytic pathways of PBMCs from long-term T1D individuals with albuminuria might be dysfunctional, possibly due to increased cellular metabolic load and/or oxidative stress in which inflammatory factors could play a role. |
| first_indexed | 2024-04-11T00:50:59Z |
| format | Article |
| id | doaj.art-447e854525704cb9a0877bf494336f07 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-11T00:50:59Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-447e854525704cb9a0877bf494336f072023-01-05T08:39:51ZengElsevierHeliyon2405-84402022-12-01812e12304Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetesJoana Mendes Lopes de Melo0Jens Christian Laursen1Niels Søndergaard-Heinrich2Ida Kirstine Bull Rasmussen3Christian Stevns Hansen4Marie Frimodt-Møller5Peter Rossing6Joachim Størling7Translational T1D Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, DenmarkComplications Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, DenmarkComplications Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, DenmarkComplications Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, DenmarkComplications Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, DenmarkComplications Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, DenmarkComplications Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, The University of Copenhagen, DK-2400, Copenhagen, DenmarkTranslational T1D Research, Clinical Research, Steno Diabetes Center Copenhagen, DK-2730, Herlev, Denmark; Department of Biomedical Sciences, University of Copenhagen, DK-2400, Copenhagen, Denmark; Corresponding author.Changes in cellular bioenergetics such as mitochondrial respiration and glycolysis may play a role in the pathogenesis of various diseases including type 1 diabetes (T1D). We used Seahorse extracellular flux technology to analyse the efficiency of glycolysis and mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells (PBMCs) obtained from fresh blood samples from fifteen long-term T1D individuals with albuminuria (five females) with an average (±SD) age of 58 (±14) years and 15 age and sex-matched healthy non-diabetic controls. In T1D PBMCs, mitochondrial proton leak was higher (T1D: 21,3 ± 1,46 pmol/min; controls: 17,3 ± 1,24 pmol/min; p = 0,049) and glucose (5 mM) suppressed mitochondrial proton leak more than in healthy controls. Further, PBMCs from T1D individuals had higher glycolysis compared with healthy controls (T1D: 9,68 ± 0,94 mpH/min; controls: 7,07 ± 0,64 mpH/min; p = 0,032). Correlation analysis of circulating inflammatory factors identified Leukaemia Inhibitor factor 1 (LIF) being negatively correlated with PBMC glycolysis. Our results suggest that mitochondrial and glycolytic pathways of PBMCs from long-term T1D individuals with albuminuria might be dysfunctional, possibly due to increased cellular metabolic load and/or oxidative stress in which inflammatory factors could play a role.http://www.sciencedirect.com/science/article/pii/S2405844022035927Type 1 diabetes (T1D)Peripheral blood mononuclear cells (PBMCs)Cellular bioenergeticsSeahorse extracellular flux technologyGlycolysisMitochondrial oxidative phosphorylation |
| spellingShingle | Joana Mendes Lopes de Melo Jens Christian Laursen Niels Søndergaard-Heinrich Ida Kirstine Bull Rasmussen Christian Stevns Hansen Marie Frimodt-Møller Peter Rossing Joachim Størling Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetes Heliyon Type 1 diabetes (T1D) Peripheral blood mononuclear cells (PBMCs) Cellular bioenergetics Seahorse extracellular flux technology Glycolysis Mitochondrial oxidative phosphorylation |
| title | Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetes |
| title_full | Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetes |
| title_fullStr | Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetes |
| title_full_unstemmed | Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetes |
| title_short | Increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type-1-diabetes |
| title_sort | increased mitochondrial proton leak and glycolysis in peripheral blood mononuclear cells in type 1 diabetes |
| topic | Type 1 diabetes (T1D) Peripheral blood mononuclear cells (PBMCs) Cellular bioenergetics Seahorse extracellular flux technology Glycolysis Mitochondrial oxidative phosphorylation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022035927 |
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