ABSTRACT
This chapter deals in particular with glutathione peroxidase 1 (GPx1) as a modulator of both insulin production and signaling, and discusses potential implications for its dual and somewhat paradoxical roles in diabetes. The family of glutathione peroxidase (GPx) enzymes, catalyzing the glutathione-dependent reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively, comprises eight mammalian isoforms. Insulin is produced and secreted solely by beta cells in the Langerhans islets of the pancreas. When GPx1 knockout (KO) mice were exposed to metabolic stress by feeding them an obesogenic high-fat diet, they developed more severe symptoms of a defective pancreatic insulin production/secretion than their wild-type littermates. GPx1 is expressed in each of the three major insulin target tissues, with the highest GPx1 protein levels and specific activities measured in the liver, compared to moderate levels in white adipose tissue and relatively low levels in skeletal muscle.
