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bioRxiv · 10.1101/2024.09.23.614422

Dense but not alpha granules of platelets are required for insulin secretion from pancreatic beta cells

Kolczynska-Matysiak, K.·Karwen, T.·Loeffler, M.·Hawro, I.·Kassouf, T.·Stegner, D.·Sumara, G.
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Abstract

ObjectivesPlatelets, originally described for their role in blood coagulation, are now also recognized as key players in modulating inflammation, tissue regeneration, angiogenesis, and carcinogenesis. Recent evidence suggests that platelets also influence insulin secretion from pancreatic {beta} cells. The multifaceted functions of platelets are mediated by the factors stored in their alpha granules (AGs) and dense granules (DGs). AGs primarily contain proteins, while DGs are rich in small molecules, and both types of granules are released during blood coagulation. Specific components stored in AGs and DGs are implicated in various inflammatory, regenerative, and tumorigenic processes. However, the relative contributions of AGs and DGs to the regulation of pancreatic {beta} cell function have not been previously explored. MethodsIn this study, we utilized mouse models deficient in AG content (neurobeachin-like 2 (Nbeal2) -deficient mice) and models with defective DG release (Unc13d-deficiency in bone marrow-derived cells) to investigate the impact of platelet granules on insulin secretion from pancreatic {beta} cells. ResultsOur findings indicate that AG deficiency has little to no effect on pancreatic {beta} cell function and glucose homeostasis. Conversely, mice with defective DG release exhibited glucose intolerance and reduced insulin secretion. Furthermore, Unc13d-deficiency in hematopoietic stem cells led to a reduction in adipose tissue gain in obese mice. ConclusionsObtained data suggest that DGs, but not AGs, mediate the influence of platelets on pancreatic {beta} cells, thereby modulating glucose metabolism.

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Kolczynska-Matysiak, K., Karwen, T., Loeffler, M., Hawro, I., Kassouf, T., Stegner, D., Sumara, G.. 2024-09-24. Dense but not alpha granules of platelets are required for insulin secretion from pancreatic beta cells. https://doi.org/10.1101/2024.09.23.614422

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