Impaired hypoxia-inducible factor (HIF) regulation by hyperglycemia.

The mechanisms that contribute to the development of diabetes complications remain unclear. A defective reaction of tissues to hypoxia has recently emerged as a new pathogenic mechanism and consists of a complex repression of hypoxia-inducible factor (HIF), which is the main regulator of the adaptive response to hypoxia. This paper discusses the mechanisms by which hyperglycaemia contributes to HIF repression in diabetes. Furthermore, a comprehensive analysis of the functional relevance of these new findings to the development of chronic diabetes complications is provided, along with examples from animal models and clinics.