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,...

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Main Authors: Schön, Martin (Author) , Oehler, Daniel (Author) , Yurchenko, Iryna (Author) , Lang, Alexander (Author) , Trinks, Nina (Author) , Dewidar, Bedair (Author) , Mastrototaro, Lucia (Author) , Zaharia, Oana P. (Author) , Bódis, Kálmán B. (Author) , Karusheva, Yanislava (Author) , Toledo, Frederico G.S. (Author) , Burkart, Volker (Author) , Granata, Cesare (Author) , Westenfeld, Ralf (Author) , Polzin, Amin (Author) , Kelm, Malte (Author) , Wagner, Robert (Author) , Roden, Michael (Author) , Szendrödi, Julia (Author)
Format: Article (Journal)
Language:English
Published: March 2026
In: Diabetes
Year: 2026, Volume: 75, Issue: 3, Pages: 571-581
ISSN:1939-327X
DOI:10.2337/db25-0625
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.2337/db25-0625
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Author Notes:Martin Schön, Daniel Oehler, Iryna Yurchenko, Alexander Lang, Nina Trinks, Bedair Dewidar, Lucia Mastrototaro, Oana P. Zaharia, Kálmán B. Bódis, Yanislava Karusheva, Frederico G.S. Toledo, Volker Burkart, Cesare Granata, Ralf Westenfeld, Amin Polzin, Malte Kelm, Robert Wagner, Michael Roden, and Julia Szendroedi, for the German Diabetes Study Group
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Summary: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.
Item Description:Veröffentlicht: 21. Januar 2026
Gesehen am 10.04.2026
Physical Description:Online Resource
ISSN:1939-327X
DOI:10.2337/db25-0625