Type 1 Diabetes (T1D) negatively influences skeletal muscle health, however, its impact on muscle satellite cells (SCs) remains largely unknown. SCs from T1D rodent (Akita) and human samples were examined to discern differences in SC density and functionality compared to their respective controls. Examination of the Notch pathway was undertaken to investigate its role in changes to SC functionality. Compared to controls, Akita mice demonstrated increased muscle damage following eccentric exercise, along with a decline in SC density and myogenic capacity. Quantification of components of the Notch signalling pathway revealed a persistent activation of Notch signalling in Akita SCs, which could be reversed with the Notch inhibitor DAPT. Similar to Akita samples, T1D human skeletal muscle displayed a significant reduction in SC content and the Notch ligand, DLL1, was significantly increased compared to controls- supporting the dysregulated Notch pathway observed in Akita muscles. These data indicate that persistent activation in Notch signalling impairs SC functionality in the T1D muscle, resulting in a decline in SC content. Given the vital role played by the SC in muscle growth and maintenance, these findings suggest that impairments in SC capacities play a primary role in the skeletal muscle myopathy that characterizes T1D.
- Received November 16, 2015.
- Accepted June 15, 2016.
- © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.