Bioinformatic Analyses of Altered Regulation of myo‐Inositol Oxygenase in Diabetes Mellitus

Abstract

In humans, myo‐inositol (MI) is catabolized by myo‐inositol oxygenase (MIOX). Depletion of MI is seen in tissues affected by diabetes mellitus such as kidney, nerve and retina. Up‐regulation of MIOX is a likely mechanism of MI depletion in these tissues. This study examines three possible mechanisms for up‐regulation of MIOX: 1) DNA regulatory elements, 2) additional copies of the gene, 3) alternate splicing resulting in other active isoforms. In silico experiments revealed known and novel regulatory elements in the MIOX gene, which are also present in other genes up‐regulated in diabetes, such as aldose reductase. A genomic sequence 86 % identical to the MIOX gene (chromosome 22) was identified in chromosome 8. This appears to be an intronless version of the MIOX gene. Further examination of the sequence revealed a TATA box and regulatory elements, but translation of the sequence resulted in short peptides with minimal identity with MIOX protein. So, this sequence may be considered a pseudogene. This study has also identified four physiologically relevant alternate splice events in MIOX transcripts evident in the EST database. The amino acid sequences of the translated products of these transcripts retain high percent identity with the known MIOX protein. Structural analyses of MIOX protein and its isoforms will indicate whether the isoforms are more active than the known MIOX protein.