Intrinsic muscle stem cell dysfunction underlies functional deficits in models of type 1 diabetes

Area of Science:

• Muscle stem cell biology
• Diabetes complications
• Skeletal muscle physiology

Background:

• Type 1 diabetes is known to impair muscle function and regeneration.
• The direct role of muscle stem cell (MuSC) dysfunction in these deficits remains unclear.

Purpose of the Study:

• To investigate whether muscle stem cell dysfunction contributes to impaired muscle function and regeneration in type 1 diabetes.
• To determine the impact of hyperglycemia on MuSC function and skeletal muscle capacity.

Main Methods:

• Utilized three-dimensional MuSC cultures (micromuscles) to assess stem cell function.
• Employed mouse models of type 1 diabetes to evaluate muscle regeneration and function after injury.
• Assessed myotube hypertrophy in vitro and in vivo.

Main Results:

• Hyperglycemia directly impairs MuSC function, leading to reduced force production in differentiated myotubes.
• MuSC dysfunction in diabetic mice correlated with poor muscle regeneration and declining functional capacity.
• Aberrant MuSC activation and loss of cell number exacerbated regeneration deficits.
• Early treatment with dapagliflozin rescued MuSC function and number, indicating hyperglycemia as the driver.

Conclusions:

• Muscle stem cell dysfunction is a key contributor to muscle functional deficits observed in type 1 diabetes.
• Hyperglycemia directly impacts MuSC number and function, compromising skeletal muscle repair and performance.
• Targeting hyperglycemia may be a viable strategy to preserve muscle health in individuals with type 1 diabetes.