Proinsulin C-Peptide Enhances Cell Survival and Protects against Simvastatin-Induced Myotoxicity in L6 Rat Myoblasts

Area of Science:

• Biochemistry
• Cell Biology
• Endocrinology

Background:

• Skeletal muscle satellite cells (SC) have reduced repair capacity in Type 1 diabetes mellitus (T1DM), leading to functional loss.
• C-peptide deficiency in T1DM impairs skeletal muscle growth and repair, contributing to morbidity.
• Statins, cholesterol-lowering drugs, are linked to increased risk of skeletal muscle dysfunction.

Purpose of the Study:

• To investigate the hypothesis that C-peptide activates signaling pathways in myoblasts, promoting survival and protecting against simvastatin-induced toxicity.
• To elucidate the role of C-peptide in mitigating simvastatin-induced myotoxicity in L6 rat myoblast cell line.

Main Methods:

• Investigated the effects of C-peptide on L6 rat myoblast cell line under serum-starved conditions.
• Assessed the impact of C-peptide on MAP kinase (ERK1/2) and Akt signaling pathways.
• Evaluated C-peptide's protective effect against simvastatin-induced apoptosis and its influence on reactive oxygen species (ROS) production.

Main Results:

• C-peptide stimulated intracellular signaling pathways (ERK1/2 and Akt) at low concentrations (0.03 nM).
• 3 nM C-peptide significantly suppressed simvastatin-induced apoptosis via a pertussis toxin-sensitive pathway.
• Simvastatin impaired Akt signaling and increased ROS production, highlighting their role in statin-induced myoblast apoptosis.

Conclusions:

• C-peptide demonstrates a significant protective effect against death signaling in myoblasts.
• C-peptide deficiency in T1DM may exacerbate myopathy by increasing progenitor cell susceptibility to insults like simvastatin.
• C-peptide's signaling activation and protective actions offer potential therapeutic insights for T1DM-related muscle dysfunction.