Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes.

ABSTRACT:

Aims/hypothesis

The conserved hypoxia inducible factor 1 α (HIF1α) injury-response pro-survival pathway has recently been implicated in early beta cell dysfunction but slow beta cell loss in type 2 diabetes. We hypothesised that the unexplained prolonged prediabetes phase in type 1 diabetes may also be, in part, due to activation of the HIF1α signalling pathway.

Methods

RNA sequencing (RNA-Seq) data from human islets with type 1 diabetes or after cytokine exposure in vitro was evaluated for activation of HIF1α targets. This was corroborated by immunostaining human pancreases from individuals with type 1 diabetes for 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), the key effector of HIF1α-mediated metabolic remodelling, and by western blotting of islets and I

SUBMITTER: Nomoto H 

PROVIDER: S-EPMC6945783 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature