title: Decreased Satellite Cell Number and Function in Humans and Mice With Type 1 Diabetes Is the Result of Altered Notch Signaling.
abstract: Type 1 diabetes (T1D) negatively influences skeletal muscle health; however, its effect on muscle satellite cells (SCs) remains largely unknown. SCs from samples from rodents (Akita) and human subjects with T1D were examined to discern differences in SC density and functionality compared with samples from their respective control subjects. Examination of the Notch pathway was undertaken to investigate its role in changes to SC functionality. Compared with controls, Akita mice demonstrated increased muscle damage after eccentric exercise along with a decline in SC density and myogenic capacity. Quantification of components of the Notch signaling pathway revealed a persistent activation of Notch signaling in Akita SCs, which could be reversed with the Notch inhibitor DAPT. Similar to Akita samples, skeletal muscle from human subjects with T1D displayed a significant reduction in SC content, and the Notch ligand, DLL1, was significantly increased compared with control subjects, supporting the dysregulated Notch pathway observed in Akita muscles. These data indicate that persistent activation in Notch signaling 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.
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Donna M
authors.initials: DM
authors.lastname: D'Souza
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Irena A
authors.initials: IA
authors.lastname: Rebalka
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Blair
authors.initials: B
authors.lastname: MacDonald
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Moradi
authors.affiliation: Department of Kinesiology, University of Windsor, Windsor, Ontario, Canada.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Krause
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Dhuha
authors.initials: D
authors.lastname: Al-Sajee
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Punthakee
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada hawke@mcmaster.ca.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hawke
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch