Prion protein modulates glucose homeostasis by altering intracellular iron.

ABSTRACT: The prion protein (PrP^C), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrP^C on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP^-/-) were significantly lower than wild type (PrP^+/+) controls. Silencing of PrP^C in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrP^C-dependent ma

SUBMITTER: Ashok A 

PROVIDER: S-EPMC5919926 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature