Manganese Acts upon Insulin/IGF Receptors to Phosphorylate AKT and Increase Glucose Uptake in Huntington's Disease Cells.

ABSTRACT: Perturbations in insulin/IGF signaling and manganese (Mn²⁺) uptake and signaling have been separately reported in Huntington's disease (HD) models. Insulin/IGF supplementation ameliorates HD phenotypes via upregulation of AKT, a known Mn²⁺-responsive kinase. Limited evidence both in vivo and in purified biochemical systems suggest Mn²⁺ enhances insulin/IGF receptor (IR/IGFR), an upstream tyrosine kinase of AKT. Conversely, Mn²⁺ deficiency impairs insulin release and associated glucose tolerance in vivo. Here, we test the hypothesis that Mn²⁺-dependent AKT signaling is predominantly mediated by direct Mn²⁺ activation of the insulin/IGF receptors, and HD-related impairments in insulin/IGF signaling are due to HD genotype-assoc

SUBMITTER: Bryan MR 

PROVIDER: S-EPMC7062569 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature