Reduced Acrolein Detoxification in akr1a1a Zebrafish Mutants Causes Impaired Insulin Receptor Signaling and Microvascular Alterations.

ABSTRACT: Increased acrolein (ACR), a toxic metabolite derived from energy consumption, is associated with diabetes and its complications. However, the molecular mechanisms are mostly unknown, and a suitable animal model with internal increased ACR does not exist for in vivo studying so far. Several enzyme systems are responsible for acrolein detoxification, such as Aldehyde Dehydrogenase (ALDH), Aldo-Keto Reductase (AKR), and Glutathione S-Transferase (GST). To evaluate the function of ACR in glucose homeostasis and diabetes, akr1a1a^-/- zebrafish mutants are generated using CRISPR/Cas9 technology. Accumulated endogenous acrolein is confirmed in akr1a1a^-/- larvae and livers of adults. Moreover, a series of experiments are performed regarding organic alterations, the glucose hom

SUBMITTER: Qi H 

PROVIDER: S-EPMC8456208 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature