Hypoxia and hypoxia-inducible factors in diabetes and its complications

• Published in: Diabetologia Vol. 64; no. 4; pp. 709 - 716
• Main Authors: Catrina, Sergiu-Bogdan, Zheng, Xiaowei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2021; Springer Nature B.V
• Subjects: Animals; Apoptosis Regulatory Proteins - metabolism; Basic Helix-Loop-Helix Transcription Factors - metabolism; Blood Glucose - metabolism; Cell Hypoxia; Cellular Microenvironment; Diabetes; Diabetes Complications - drug therapy; Diabetes Complications - metabolism; Diabetes Complications - physiopathology; Diabetes mellitus; Diabetes Mellitus - drug therapy; Diabetes Mellitus - metabolism; Diabetes Mellitus - physiopathology; Diabetic nephropathy; Diabetic neuropathy; Diabetic retinopathy; Foot diseases; Homeostasis; Human Physiology; Humans; Hyperglycemia; Hypoglycemic Agents - therapeutic use; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Hypoxia-inducible factors; Insulin resistance; Internal Medicine; Leg ulcers; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metabolic Diseases; Molecular Targeted Therapy; Oxygen - metabolism; Prolyl-Hydroxylase Inhibitors - therapeutic use; Repressor Proteins - metabolism; Review; Signal Transduction; Diabetic retinopathy; Prolyl hydroxylase inhibitor; Diabetes complications; Hypoxia-inducible factor; Diabetic nephropathy; Hypoxia; Insulin resistance; Diabetes; Review; Diabetic foot ulcer
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-021-05380-z

Hypoxia-inducible factors (HIFs) are the key regulators of oxygen homeostasis in response to hypoxia. In diabetes, multiple tissues are hypoxic but adaptive responses to hypoxia are impaired due to insufficient activation of HIF signalling, which results from inhibition of HIF-1α stability and function due to hyperglycaemia and elevated fatty acid levels. In this review, we will summarise and discuss current findings about the regulation of HIF signalling in diabetes and the pathogenic roles of hypoxia and dysregulated HIF signalling in the development of diabetes and its complications. The therapeutic potential of targeting HIF signalling for the prevention and treatment of diabetes and related complications is also discussed. Graphical abstract