Elucidating the Role of Glycogen in Glucose Transporter 1 Deficiency Syndrome

Abstract

Glucose Transporter 1 Deficiency Syndrome (G1D) is a rare genetic disorder characterized by impaired brain glucose metabolism caused by mutations in the SLC2A1 gene. Mutations in the SLC2A1 gene lead to reduced or loss of function in the glucose transporter protein type 1 (GLUT‐1), affecting its ability to deliver glucose across the blood brain barrier. This lack of glucose in the brain affects brain function and development, causing people with the disorder to suffer from seizures, learning disabilities, and struggle for independence. While decreased levels of glucose in G1D is recognized, glycogen levels in the brain have not been studied in human or animal models of the disease. We employed a mouse model of G1D syndrome characterized by a loss of function in the SLC2A1 gene to study glycogen levels. Wildtype and G1D animals of the same sex at 14 weeks old were utilized for this study. Immunohistochemical (IHC) staining with IV58B6 and an amyloglucosidase glycogen assay were used to determine regional and total glycogen levels, respectively. HALO software was employed to quantify IHC staining, and the enzymatic glycogen determination was measured with a spectrophotometric microplate reader. Through these techniques, it was determined that G1D mice had perturbed glycogen levels present in multiple regions of the brain. These data suggest that the G1D phenotype could be affected by perturbed levels of glycogen in the brain. Further research into the effect of glycogen levels in G1D may be important for determining disease modalities, defining disease progression, and understanding preclinical data and drug treatment.