Cyb5r3 links FoxO1-dependent mitochondrial dysfunction with β-cell failure.

ABSTRACT:

Objective

Diabetes is characterized by pancreatic β-cell dedifferentiation. Dedifferentiating β cells inappropriately metabolize lipids over carbohydrates and exhibit impaired mitochondrial oxidative phosphorylation. However, the mechanism linking the β-cell's response to an adverse metabolic environment with impaired mitochondrial function remains unclear.

Methods

Here we report that the oxidoreductase cytochrome b5 reductase 3 (Cyb5r3) links FoxO1 signaling to β-cell stimulus/secretion coupling by regulating mitochondrial function, reactive oxygen species generation, and nicotinamide actin dysfunction (NAD)/reduced nicotinamide actin dysfunction (NADH) ratios.

Results

The expression of Cyb5r3 is decreased in FoxO1-deficient β cells. Mice with β-cell-specific deletio

SUBMITTER: Fan J 

PROVIDER: S-EPMC7031142 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature