Caenorhabditis elegans as a diabetes and ischemia model‐ a genetic approach to understanding glucose toxicity and oxygen deprivation

Abstract

Oxygen deprivation, which is central to many human‐health related issues (Ex: stroke, cardiac and pulmonary disorders), can have a more detrimental affect on individuals who are diabetic or obese. We are using the genetic model system, Caenorhabditis elegans, to examine how environment (Ex: carbohydrate diet) influences oxygen deprivation response and survival. Our lab examines oxygen deprivation responses at various stages of development including aging adults. Wild‐type C. elegans fed the standard diet can survive severe oxygen deprivation for at least 24 hours however this survival rate is severely decreased if raised on an enriched carbohydrate diet or if exposed to longer periods of oxygen deprivation. Taking a genetic approach with the analysis of mutants we determined that the following signaling pathways influence anoxia survival: insulin‐like signaling, developmental pathways that alter germline function, carbohydrate metabolism, hexosamine signaling and methylglycoxal protein modification. Furthermore, pretreatment with the diabetic drug metformin enhances anoxia survival. These results support the idea that C. elegans is a powerful model system to further investigate at the molecular level why a particular diet can lead to susceptibility to oxygen deprivation.