Platelet glycogenolysis is important for energy production and function

Area of Science:

• Biochemistry
• Hematology
• Metabolic disorders

Background:

• Glycogen presence in platelets is known since the 1960s, but its functional significance remains largely undetermined.
• Glycogen storage diseases and glycogen phosphorylase inhibitors are associated with bleeding tendencies, suggesting a role for platelet glycogen in hemostasis.

Purpose of the Study:

• To investigate the impact of glycogen mobilization on platelet function.
• To elucidate the role of glycogen as a metabolic fuel in platelet activation and hemostasis.

Main Methods:

• Utilized glycogen phosphorylase (GP) inhibitors (CP316819 and CP91149) to block glycogen breakdown.
• Performed ex vivo platelet assays including activation, secretion, aggregation, and clot contraction.
• Conducted Seahorse energy flux analysis and metabolite supplementation experiments.

Main Results:

• Inhibition of GP activity led to increased glycogen levels in resting and activated platelets.
• Blocking glycogen mobilization significantly inhibited platelet secretion and clot contraction.
• Platelet aggregation was minimally affected, while energy metabolism was influenced by glycogen availability and external fuels.

Conclusions:

• Platelet glycogen serves as a critical metabolic fuel source, particularly important for secretion and clot contraction.
• Impaired glycogen mobilization contributes to bleeding diathesis observed in glycogen storage diseases.
• Findings offer insights into potential effects of hyperglycemia and diabetes treatments on platelet function and hemostasis.