The longstanding theory is that diabetic kidney disease is the result of a chain of events — high blood sugar causes mitochondria within our cells to produce an excess of superoxide anion that is highly toxic and reactive to cells; this results in cellular damage which causes organ dysfunction and disease. However, new research suggests that the opposite is true when it comes to chronic hyperglycemia caused by diabetes.
Researchers from the University of California, San Diego tested diabetic mice for levels of superoxide anion in their damaged kidneys and found they actually had reduced superoxide levels. Then, upon stimulation of an enzyme in the mitochondria known as AMP-activated protein kinase (AMPK), a vital energy-sensing enzyme in the mitochondria, superoxide production increased but then remarkably the evidence of kidney disease decreased. This suggests that by increasing mitochondrial activity and, thus, superoxide activity, there would be a benefit in diabetic kidney disease.
The reduction in AMPK activity seen in diabetic kidney disease is likely a result of caloric excess which can lead to events such as inflammation or fibrosis and that by exercising and losing weight as well as reducing caloric intake we can increase beneficial AMPK activity. AMPK is known to stimulate muscle glucose uptake, fatty acid oxidation, and modulation of insulin secretion by beta-cells in the pancreas. Research is ongoing as to whether there is a pharmacologic basis for modulating AMPK activity for diabetes.
- Previous theory suggested increased mitochondrial activity (AMPK specifically) leads to increased superoxide anion which causes kidney damage and dysfunction.
- New animal model research suggests the opposite is true, that diabetics have decreased superoxide and AMPK activity which damages the kidneys.
- By making lifestyle changes like exercise and caloric intake reduction we can boost the beneficial AMPK activity of the mitochondria, thus preserving the kidneys.