Role of sphingolipids in muscle repair and function in humans and mice; Role of Type 1 diabetes in sphingolipid levels

Role of sphingolipids in muscle repair and function in humans and mice; Role of Type 1 diabetes in sphingolipid levels

Role of sphingolipids in muscle repair and function in humans and mice; Role of Type 1 diabetes in sphingolipid levels


Dr. Matthew Krause

University of Windsor



SPONSOR: Faculty of Human Kinetics, University of Windsor; Office of Research and Innovation Services, University of Windsor

GRANT DURATION: 2021-2022



Related Programs:
Nucleus Cores:

Maintaining a healthy, functional skeletal mass is essential to our well-being, while loss of skeletal muscle mass and/or quality is strongly linked to increased morbidity and mortality in several clinical conditions. While the mechanisms of skeletal muscle loss in disease are diverse, it is worth considering the following characteristics of muscle tissue: 1) it has a robust capacity for repair following injury/damage due to numerous stem and progenitor cell populations, 2) it is influenced by exercise and chronic disease, 3) it is highly sensitive to extracellular cues including growth factors, extracellular matrix ligands, and signalling lipids and 4) it requires vascular supply and innervation for normal function and successful repair.

Tissue repair (healing) is essential to maintain optimal body function. Resulting from heavy physical work (exercise, occupation-related), skeletal muscle damage must be repaired to maintain contractile function in the long-term. A vast, orderly cellular response (e.g., inflammatory cells invasion of damaged tissue, breakdown and reformation of the extracellular matrix, cytokine and growth factor release) removes damaged tissue, stimulates the generation of new tissue and promotes successful healing and restoration of muscle function. While much has already been established regarding skeletal muscle repair, the pathophysiological mechanisms underlying poor muscle repair in aging or disease states are not well understood.

Diabetic myopathy refers to the pathophysiological state of skeletal muscle in diabetes. In particular, diabetic myopathy in type 1 diabetes mellitus (T1D) has been characterized and it has been established that muscle repair is compromised. While some mechanisms have been identified, much is still left to be understood. Specific to this proposal, the role of a family of biologically active signalling lipids, the sphingolipids, have not been investigated in the context of diabetic myopathy in T1D. The sphingolipids are of interest because many have been identified as influential to the muscle repair process, insulin signalling, and vascular function, all of which are negatively affected in diabetes. 

Impact

The major objective of this study is to ascertain the levels of sphingolipids in blood in both T1D people and a commonly used murine model of T1D, the Akita mouse. Further, a secondary objective is to take measures of reactive hyperemia (blood flow response following brief arterial occlusion) in T1D to detect any correlations in muscle bed microvascular dilatory function with sphingolipid species levels.


Events

 


This team presented their research project at the WE-SPARK Cheers to Hope event in May of 2023.


CO-INVESTIGATORS

University of Windsor

  • Dr. Anthony Bain
Loading...