AKR1B1 and diabetes mellitus: Our data suggest that long-term epigenetic modification of the Igf-1 gene was not responsible for the binding of these transcription factors since (1) the diabetes-induced downregulation of IGF-1 was readily reversible with a return to normoglycemia, blockade of aldose reductase activity by sorbinil, or treatment with IGF or LDGF (Fig. 2G–I, Supplemental Figure 2), and (2) our DNA methylation data for the IGF-1 promoter in DRG revealed no significant alterations under diabetic conditions, although there was an increase at cpg5 (Supplemental Figure 5C).