12:00 AM
Jun 10, 2010
 |  BC Innovations  |  Cover Story

Unique pathway in diabetes

A North American team has identified a proinflammatory pathway involving eukaryotic translation initiation factor 5A, a poorly understood translational initiation factor, as a potential player in diabetes.1Senesco Technologies Inc., which collaborated on the study, has a pancreas-specific formulation of a eukaryotic translation initiation factor 5A small interfering RNA in preclinical development for diabetes. Cytokine PharmaSciences Inc.has a Phase II-ready anti-inflammatory compound that may also block the pathway.

Eukaryotic translation initiation factor 5A (EIF5A) is "somewhat enigmatic, in that we haven't understood what its normal role is," said Raghavendra Mirmira, professor of pediatrics and medicine at the Indiana University School of Medicine. He is the corresponding author on the paper in The Journal of Clinical Investigation that describes the findings.

EIF5A undergoes a unique post-translational modification in which a single lysine residue is converted into an unconventional amino acid called hypusine that is found nowhere else in nature. This conversion requires the sequential activity of two enzymes: deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase/monooxygenase (DOHH).

Although mouse knockouts have shown that Eif5a hypusination is not essential for survival under most circumstances, work published in 2008 suggested that Eif5a promoted lung inflammation and sepsis in mice.2

Because many proinflammatory pathways are at play in the pancreas in both type 1 and type 2 diabetes, the researchers...

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