Abstract
Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (i.e., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of ex vivo assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited platelet secretion and clot contraction, with minimal effects on aggregation. Seahorse energy flux analysis and metabolite supplementation experiments suggested that glycogen is an important metabolic fuel whose role is affected by platelet activation and the availability of external glucose and other metabolic fuels. Our data shed light on the bleeding diathesis in glycogen storage disease patients and offer insights into the potential effects of hyperglycemia on platelets.
Document Type
Article
Publication Date
2023
Digital Object Identifier (DOI)
https://doi.org/10.1080/09537104.2023.2222184
Funding Information
The work was supported by grants from the NIH, NHLBI [HL56652, HL138179, and HL150818], and a Department of Veterans Affairs Merit Award to S.W.W.
Repository Citation
Prakhya, Kanakanagavalli Shravani; Vekaria, Hemendra J.; Coenen, Daniёlle M.; Omali, Linda; Lykins, Joshua; Joshi, Smita; Alfar, Hammodah Rawhi Hammodah; Wang, Qing Jun; Sullivan, Patrick G.; and Whiteheart, Sidney W., "Platelet glycogenolysis is important for energy production and function" (2023). Saha Cardiovascular Research Center Faculty Publications. 67.
https://uknowledge.uky.edu/cvrc_facpub/67
Notes/Citation Information
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.