Background:
Diabetic kidney disease (DKD) affects approximately one third of people with diabetes, greatly increasing the chance of cardiovascular disease and mortality. Current treatment strategies are limited to partially slowing down disease progression.
Mitochondrial dysfunction has been shown to be an important factor in the development and progression of DKD, with the high metabolic demands imposed by diabetes overwhelming the kidney’s capacity to produce sufficient energy.
Here we propose that a portion of the people more susceptible to developing DKD may have underlying mitochondrial deficiencies and test the efficacy of a novel treatment designed to improve mitochondrial function, here named MitoA, in preventing the onset and/or severity or DKD in a mouse model of Type 1 Diabetes.
Methods
Mice, both wildtype and NDUFS6+/- (mitochondrial protein in electron transport chain), where induced with Type 1 diabetes (T1D) using streptozotocin and administered with “MitoA”, a drug targeted at improving mitochondrial function. Blood glucose control was assessed by taking weekly BG levels, performing an oral glucose tolerance test (OGTT) and by measuring HbA1c levels. Kidney function/damage was assessed by measuring the glomerular filtration rate (via clearance of FITC-sinistrin), the albumin to creatinine ratio (uACR) and via histology (e.g., the glomerular sclerosis index).
Results
The diabetic mice with genetically exposed mitochondrial dysfunction (NDUFS6+/-) had a decreased weekly area under the curve (AUC) for blood glucose levels (P=0.006) and for the OGTT blood glucose AUC (P=0.0006), with the treatment showing no statistically significant effect.
Conclusion
Increasing our understanding of the role of dysfunctional mitochondria in DKD progression may provide new, much needed therapeutics to halt the progression of kidney damage in people with diabetes.