Targeting PKCα alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.

ABSTRACT:

Abstract

Ferroportin (Fpn) is the only iron exporter, playing a crucial role in systemic iron homeostasis. Fpn is negatively regulated by its ligand hepcidin, but other potential regulators in physiological and disease conditions remain poorly understood. Diabetes is a metabolic disorder that develops body iron loading with unknown mechanisms. By using diabetic mouse models and human duodenal specimens, we demonstrated that intestinal Fpn expression was increased in diabetes in a hepcidin-independent manner. Protein kinase C (PKC) is hyperactivated in diabetes. We showed that PKCα was required to sustain baseline Fpn expression and diabetes-induced Fpn upregulation in the enterocytes and macrophages. Knockout of PKCα abolished diabetes-associated iron overload. Mechanistically, act

SUBMITTER: Banerjee S 

PROVIDER: S-EPMC11451300 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature