Integrating SMRT and Bulk RNA Sequencing With Metabolic Phenotyping to Examine Reduced Skeletal Muscle Mitochondrial Respiration in Type 2 Diabetes
In our study, we developed a pipeline to integrate single-molecule real-time sequencing (SMRT-seq) with comprehensive metabolic phenotyping to examine reduced mitochondrial respiration in the skeletal muscle of individuals with type 2 diabetes. SMRT-seq revealed ∼67,000 isoforms originating from ∼14,000 unique genes; the isoform numbers per gene did not differ between participants with diabetes and matched control participants. Our data identified novel alternative splicing events, including two variants of the ATP5F1A gene encoding a subunit for ATP synthase. Among these, two novel transcripts were expressed exclusively in control participants. Our findings link transcriptomic changes to impaired mitochondrial respiration in type 2 diabetes, with the potential of providing novel therapeutic targets to improve metabolic health.
Authors
- Yanislava Karusheva (ORCID: https://orcid.org/0000-0002-4000-7894)
- Bedair Dewidar (ORCID: https://orcid.org/0000-0002-6678-0818)
- Iryna Yurchenko
- Gertjan Geerling (ORCID: https://orcid.org/0000-0002-0017-599X)
- Oana Zaharia
- Kuss Oliver
- V Burkart
- Ralf Westenfeld (ORCID: https://orcid.org/0000-0001-7058-3051)
- Jörg Kotzka (ORCID: https://orcid.org/0000-0003-1173-9372)
- Daniel Oehler (ORCID: https://orcid.org/0000-0002-0435-4119)
- Nina Trinks (ORCID: https://orcid.org/0000-0003-2540-1444)
- K Bódis
- Lucia Mastrototaro (ORCID: https://orcid.org/0000-0003-3604-6636)
- GJ Bönhof
- Amin Polzin
- Michael Roden
- Malte Kelm
- German Diabetes Study group*
- Vera Schrauwen-Hinderling
- Andrea Icks
- Alexander Lang
- Martin Schön
- Cesare Granata
- Robert Wagner
- Frederico G S Toledo
- Julia Szendroedi
- W. Rathmann
- B. Belgardt
- C. Herder
- S. Schlesinger
- K. Jandeleit-Dahm
- H. Al-Hasani
- J. Szendroedi
- S. Trenkamp
- R. Wagner
- M. Roden
- E. Lammert
Institutions
- University of Pittsburgh (US)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Düsseldorf University Hospital (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Diabetes
- Published
- 2026-01-21
- DOI
- https://doi.org/10.2337/db25-0625
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Eli Lilly and Company
- AstraZeneca
- Sanofi
- Deutsches Krebsforschungszentrum
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Bundesministerium für Gesundheit
- Novo Nordisk