Understandig the Glycemic Benefit of Pantothenate Kinase 4 (PanK 4) in Skeletal Muscle

Contact: Adriana Miranda Cervantes

Funding: German Research Foundation (DFG)

MPM-Abbildung Forschungsthema 1 (Quelle: M. Kleinert)
Elucidating a Novel Exercise-Responsive Signaling Pathway for Metabolic Health in Muscle: In preliminary work we have shown that PanK4 is sufficient to increase glucose uptake in muscle. In the project, we want to understand if PanK4 is necessary for exercise/contraction-induced glucose uptake, how PanK4 is activated and what it signals to in skeletal muscle. (Source: M. Kleinert)

We recently described the enormous complexity of the exercise-stimulated signaling network in our collaborative study of global protein phosphorylation status in biopsies from human skeletal muscle (Hoffman et al., 2015). In response to an intense session of bicycling, approximately 1,000 phosphorylation sites were significantly regulated, of which >90% were previously unknown to be exercise-responsive (Hoffman et al., 2015). Thus, only a small fraction of the molecules regulating exercise-stimulated processes such as glucose uptake have thus far been identified and numerous exciting discoveries lie ahead.

Our group integrated published human and mouse exercise phosphoproteomic and proteomic data (Kleinert et al., 2017 and Kleinert et al., 2018) with additional unpublished data to create a discovery platform of particular exciting and conserved novel exercise hits. This identified the pantothenate kinase 4 (PanK4). In preliminary work we have shown that muscle-specific overexpression of PanK4 improves glucose uptake into mouse skeletal muscle, while muscle-specific deletion of PanK4 causes insulin resistance. This identifies PanK4 as a potentially important new therapeutic target to improve skeletal muscle insulin resistance. Especially considering that PanK4 is highly abundant in human skeletal muscle. In a DFG-funded project, using novel loss-of function mouse models, we are now exploring the molecular and physiological function of PanK4 in skeletal muscle in the context of exercise and insulin stimulating.