Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila.
Insulin-degrading enzyme (IDE) is implicated in the pathogenesis of type 2 diabetes mellitus (DM2) and Alzheimer's disease (AD). Here we provide genetic evidence that Drosophila Ide (dIde) antagonizes the insulin signaling pathway and human Abeta-induced neurotoxicity in Drosophila. In this study, we also generated a dIde knockout mutant (dIde(KO)) by gene targeting, and found that loss of IDE increases the content of the major insect blood sugar, trehalose, thus suggesting a conserved role of IDE in sugar metabolism. Using dIde(KO) as a model, further investigations into the biological functions of IDE and its role in the pathogenesis of DM2 and AD can be made.
Tsuda
Manabu
M
Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan.
Kobayashi
Toshikazu
T
Matsuo
Takashi
T
Aigaki
Toshiro
T
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight; D004195:Disease Models, Animal; D004330:Drosophila; D005260:Female; D005947:Glucose / Q000378:metabolism; D006458:Hemolymph / Q000378:metabolism; D006801:Humans; D007339:Insulysin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D014199:Trehalose / Q000378:metabolism
D016229:Amyloid beta-Peptides; D014199:Trehalose; D007339:Insulysin; D005947:Glucose