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The Role of Spliceome in Skeletal Muscle Insulin Resistance

The project has made significant strides in exploring the role of the spliceome in skeletal muscle insulin resistance, particularly in high-risk diabetic individuals undergoing lifestyle interventions. Key achievements include:

  • Development and implementation of a pipeline integrating long-read RNA sequencing and proteomics for the identification of alternative splicing isoforms.
  • Successful subcellular fractionation of skeletal muscle biopsies into cytoplasmic, nuclear, and mitochondrial compartments, improving proteomic analysis quality.
  • Characterization of PGC1α isoforms into long and short categories, correlating them with mitochondrial function and insulin resistance.
  • Enhanced understanding of mitochondrial plasticity and its role in insulin resistance.

These findings provide a robust framework for future studies and potential applications in personalized medicine

 

Alternative splicing generates distinct mRNA and protein isoforms by combining different exon sequences. This figure illustrates how specific protein isoforms contribute to mitochondrial plasticity and insulin resistance, highlighting their roles in lean and insulin-resistant states. 

Copyright: Image created with BioRender and provided by Dr. Thomas Fleming, Medical Faculty Heidelberg, Heidelberg University.