MA SULLIVAN1, Z WANG1, I LI1, L MILTON1, D MCCARTHY1, BE HARCOURT2, S PENFOLD3, JM FORBES1
1Glycation and Diabetes, Mater Research Institute – The University Of Queensland, Brisbane, Australia, 2Centre for Hormone Research, Murdoch Children’s Research Institute Murdoch Children’s Research Institute, Melbourne, Australia, 3Baker Heart and Diabetes Insitute, Melbourne, Australia
Aims: To elucidate glucose/glycogen metabolism in diabetic kidneys and determine its role in kidney health and blood glucose homeostasis.
Background: Diabetes, characterised by a fundamental breakdown in glucose homeostasis, is the principle cause for kidney disease. Diabetes leads to an over-accumulation of the energy storage molecule glycogen (a highly branched polymer of glucose) in kidney tissue. This study was designed to determine the cause of this accumulation and the possible effects it has on kidney health and blood glucose control.
Methods: The amount and structural parameters of kidney glycogen from a diabetic mouse model (db/db) was analysed within the context of both kidney function and blood glucose control. Glcyogen was analysed using histology (periodic acid Schiff stain before and after diastase digestion, PASD), size exclusion chromatography, fluorophore assisted carbohydrate electrophoresis and transmission election microscopy. Kidney function was assessed by measuring the glomerular filtration rate and urinary albumin excretion rate.
Results: There were large accumulations of glycogen in the diabetic kidney, with very low amounts detected in the non-diabetic control tissue. This glycogen resembled the cell damaging “polyglucosan bodies” seen in glycogen storage diseases such as Lafora disease. While there was a correlation between glycogen accumulation and both kidney damage and poor blood glucose control, any causal links could not be determined from this initial study.
Conclusions: Diabetic mice accumulate significant quantities of abnormally structured glycogen, which correlates with poor kidney function and poor blood glucose control.
Dr Mitchell Anthony Sullivan is a CJ Martin Early Career Research Fellow, funded by the National Health and Medical Research Council (NHMRC). Mitchell has a postdoctoral position in Professor Josephine Forbes’ Glycation and Diabetes research group at the Translational Research Institute. With a keen interest in the role of the blood-sugar storage molecule glycogen in health and disease, Mitchell has used the techniques he helped develop in his PhD to examine the important role this molecule has in diseases such as diabetes, Lafora disease and Adult Polyglucosan Body Disease.