Poster Presentation ESA-SRB-ANZOS 2025 in conjunction with ENSA

Unravelling the role of glycogen in diabetic kidney disease (DKD)   (129110)

Ellen N Tejo 1 , Rani Whiddett 1 , Benjamin VK Goh 1 , Preeti Chandrasekar 1 , Domenica McCarthy 1 , Brooke J Wanrooy 2 , Conni HY Wong 2 , Josephine Forbes 1 2 3 4 , Mitchell A Sullivan 1 5 6
  1. Glycation and Diabetes Complication, Mater Research Institute - The University of Queensland, the Translational Research Institute (MRI-UQ, TRI), Brisbane, QUEENSLAND, Australia
  2. Department of Medicine, Monash University, Melbourne, Victoria, Australia
  3. Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
  4. Mater Hospital, Mater Misericordiae Ltd, Brisbane, Queensland, Australia
  5. Centre for Bioinnovation and School of Health, University of Sunshine Coast, Sippy Downs, Queensland, Australia
  6. Sunshine Coast Health Institute, Birtinya, Queensland, Australia

Diabetes is characterised by impaired glucose homeostasis and storage. This dysregulation significantly alters glycogen levels in various tissues, including the kidneys. Clinical and preclinical studies consistently report renal glycogen accumulation in diabetes, likely due to impaired glucose reabsorption from hyperglycemia. Given the kidneys' key role in glucose handling, understanding kidney glycogen's role, distribution, and significance in diabetes is essential. With over one-third of diabetic patients developing Diabetic Kidney Disease (DKD), insights into kidney glycogen metabolism may reveal novel therapeutic targets.

To investigate this, male kidney-specific Gys1 homozygous knockout (KO) mice (n=3–8/group), generated via the Cre-Flox system, were used alongside wildtype (WT) controls. Type 1 diabetes was induced using five daily intraperitoneal injections of low-dose streptozotocin (STZ, 55 mg/kg/day). Mice were provided standard chow and water ad libitum for 22 weeks before euthanasia.

The Gys1 KO model was validated by significantly reduced glycogen levels in KO diabetic mice compared to WT diabetic controls. WT diabetic mice exhibited significantly lower body weight, impaired blood glucose control (measured by glycated hemoglobin and oral glucose tolerance test), and increased Glomerular Filtration Rate (GFR, via Medibeacon FITC-sinistrin assay) and Glomerular Sclerosis Index (GSI) relative to WT non-diabetic mice. These parameters align with diabetic symptoms and early kidney damage.

There were no significant differences between KO and WT diabetic groups in body weight, glucose control, or GFR. However, the KO diabetic group showed a trend toward better glomerular health (lower GSI) compared to WT diabetic mice. This suggests that excess glycogen storage in diabetic kidneys may not directly affect glycemic control or filtration rate, but may influence glomerular structure. Further investigation is needed to determine whether kidney glycogen plays a protective, harmful, or neutral role in diabetes.