Pdgfrα deficiency in islet b-cells up-regulates apoptosis 1 of beta-cells and disturbs 2 glucose metabolism in B6 mice

We found that the Pdgfrα-deficient mice gained significantly more body weight, with more body fat, poorer glucose metabolism, and the β-cells were more apoptotic and had lower insulin content. Our further mechanistic investigations showed that Pdgfrα deletion suppressed Atf5 by down regulation of PI3K, leading to enhanced β-cell apoptosis.

Atf5 regulates Gadd45b, Bcl2 and aminoacyl-tRNA synthetase expression and alters insulin biosynthesis and glucose metabolism. Targeting these β-cell apoptotic factors may provide an opportunity for improving preventive and/or therapeutic strategies for diabetes and beyond.