Skip to ContentSkip to Navigation
Research Pediatrics
University Medical Center Groningen

New Key Publication: Hepatocyte-specific glucose-6-phosphatase deficiency disturbs platelet aggregation and decreases blood monocytes upon fasting-induced hypoglycemia

04 June 2021

Objective: Glycogen storage disease type 1a (GSD Ia) is a rare inherited metabolic disorder caused by mutations in the glucose-6-phosphatase (G6PC1) gene. When untreated, GSD Ia leads to severe fasting-induced hypoglycemia. Although current intensive dietary management aims to prevent hypoglycemia, patients still experience hypoglycemic events. Poor glycemic control in GSD Ia is associated with hypertriglyceridemia, hepatocellular adenoma and carcinoma, and also with an increased bleeding tendency of unknown origin.

Methods: To evaluate the effect of glycemic control on leukocyte levels and coagulation in GSD Ia, we employed hepatocyte-specific G6pc1 deficient (L-G6pc-/-) mice under fed or fasted conditions, to match good or poor glycemic control in GSD Ia, respectively.

Results: We found that fasting-induced hypoglycemia in L-G6pc-/- mice decreased blood leukocytes, specifically proinflammatory Ly6Chi monocytes, compared to controls. Refeeding reversed this decrease. The decrease in Ly6Chi monocytes was accompanied by an increase in plasma corticosterone levels and was prevented by the glucocorticoid receptor antagonist mifepristone. Further, fasting-induced hypoglycemia in L-G6pc-/- mice prolonged bleeding time in the tail vein bleeding assay, with reversal by refeeding. This could not be explained by changes in coagulation factors V, VII, or VIII, or von Willebrand factor. While the prothrombin and activated partial thromboplastin time as well as total platelet counts were not affected by fasting-induced hypoglycemia in L-G6pc-/- mice, ADP-induced platelet aggregation was disturbed.

Conclusions: These studies reveal a relationship between fasting-induced hypoglycemia, decreased blood monocytes, and disturbed platelet aggregation in L-G6pc-/- mice. While disturbed platelet aggregation likely accounts for the bleeding phenotype in GSD Ia, elevated plasma corticosterone decreases the levels of proinflammatory monocytes. These studies highlight the necessity of maintaining good glycemic control in GSD Ia.


  • Anouk M La Rose
  • Venetia Bazioti
  • Joanne A Hoogerland
  • Arthur F Svendsen
  • Anouk G Groenen
  • Martijn van Faassen
  • Martijn G S Rutten
  • Niels J Kloosterhuis
  • Bertien Dethmers-Ausema
  • J Hendrik Nijland
  • Gilles Mithieux
  • Fabienne Rajas
  • Folkert Kuipers
  • Michaël V Lukens
  • Oliver Soehnlein
  • Maaike H Oosterveer
  • Marit Westerterp

Read more: Molecular Metabolism :

Last modified:08 July 2021 10.09 a.m.

More news

  • 16 April 2024

    UG signs Barcelona Declaration on Open Research Information

    In a significant stride toward advancing responsible research assessment and open science, the University of Groningen has officially signed the Barcelona Declaration on Open Research Information.

  • 02 April 2024

    Flying on wood dust

    Every two weeks, UG Makers puts the spotlight on a researcher who has created something tangible, ranging from homemade measuring equipment for academic research to small or larger products that can change our daily lives. That is how UG...

  • 18 March 2024

    VentureLab North helps researchers to develop succesful startups

    It has happened to many researchers. While working, you suddenly ask yourself: would this not be incredibly useful for people outside of my own research discipline? There are many ways to share the results of your research. For example, think of a...