In This Issue of Diabetes

The massive levels of energy required by the kidneys to do their job of fi ltering what is needed or not needed may come down to one particular protein called apoptosis-inducing factor (AIF). According to Coughlan et al. (p. 1085), defi ciencies of AIF may explain many aspects of kidney disease and particularly diabetic nephropathy. Animal and human studies reveal that AIF defi ciency results in a disruption in oxidative phosphorylation and because the kidney relies on this process for homeostasis, all sorts of potentially crucial molecules might be lost to urinary excretion. The authors reveal that partially knocking out the genes related to AIF expression in mice resulted in emerging chronic kidney disease features. A series of follow-up experiments detail the likely mechanisms involved. To understand the impact of diabetes, the authors then imposed a diabetes background on the same AIF-defi cient mice and found that there were extensive changes in mitochondrial metabolism that resulted in worsening kidney damage. Subsequent experiments then focused on the kidney cells from patients with diabetes, which revealed a decrease in AIF within the renal tubular compartment and a lower level of expression of the gene AIFM1. This signifi cantly correlated with lower glomerular fi ltration rate, indicating there was a loss of kidney function. Finally, the authors write that lentiviral-induced overexpression of AIF resulted in a rescue of the kidney tubular cells and their reaction to glucose by improving the effi ciency of mitochondrial respiration. According to author Melinda T. Coughlan: “Diabetic kidney disease is associated with reduced AIF expression, however the underlying mechanisms are yet to be unraveled. This study highlights the importance of AIF in the maintenance of kidney homeostasis and further research in this area is warranted. It is possible that AIF may represent a new therapeutic target for the treatment of chronic kidney diseases, particularly diabetic kidney disease.” Rapamycin Blocks a Key Thermogenesis Pathway in White Adipose Tissue: Diabetes/Obesity Implications