The candidate is a young investigator at Mayo Clinic who is interested in how changes to skeletal muscle proteins contribute to the pathophysiology of Type 2 Diabetes. In particular, skeletal muscle mitochondria are the primary site of fuel metabolism and the development of insulin resistance with obesity appears to be linked to a decreased ability for mitochondria to function properly. His career objective is to investigate the contribution of mitochondrial function to Type 2 diabetes progression with a focus on cellular mechanisms that maintain protein health. The immediate career goal is to have protected research time to establish the connection between changes to insulin sensitivity and mitochondrial protein damage. In order to meet these goals, the candidate has developed an effective mentoring team in diabetes research (Dr. Nair), proteomics analysis by mass spectrometry (Dr. Bergen) and bioinformatics (Dr. Kocher). The training proposal includes new skills in proteomics and bioinformatics to identify damaging post-translational modifications to proteins during high fat feeding (decrease insulin sensitivity) compared to pioglitazone treatment and exercise training (increased sensitivity). The approach will establish a research theme of determining the contribution of mitochondrial dysfunction to Type 2 diabetes. The resources and career development at Mayo Clinic provide outstanding opportunity to successfully complete the proposed project. At the completion of the award, the candidate will be well suited to perform mechanistic animal studies along with translational research in humans.
Mitochondria are the primary site for fuel metabolism in skeletal muscle and the deterioration of mitochondria is implicated in the development of Type 2 diabetes. The current proposal seeks to understand how damage to mitochondrial proteins is regulated during changes to insulin resistance. It is hoped the results will help future therapies to treat or prevent Type 2 diabetes.
| Stierwalt, Harrison D; Ehrlicher, Sarah E; Bergman, Bryan C et al. (2018) Insulin-stimulated Rac1-GTP binding is not impaired by palmitate treatment in L6 myotubes. Physiol Rep 6:e13956 |
| Dasari, Surendra; Newsom, Sean A; Ehrlicher, Sarah E et al. (2018) Remodeling of skeletal muscle mitochondrial proteome with high-fat diet involves greater changes to ?-oxidation than electron transfer proteins in mice. Am J Physiol Endocrinol Metab 315:E425-E434 |
| Ehrlicher, Sarah E; Stierwalt, Harrison D; Newsom, Sean A et al. (2018) Skeletal muscle autophagy remains responsive to hyperinsulinemia and hyperglycemia at higher plasma insulin concentrations in insulin-resistant mice. Physiol Rep 6:e13810 |
| Newsom, Sean A; Miller, Benjamin F; Hamilton, Karyn L et al. (2017) Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment. Am J Physiol Endocrinol Metab 313:E552-E562 |
