1Centre for Diabetes, Obesity and Endocrinology, Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
2Westmead Hospital, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
3Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
Address correspondence to: Jenny E. Gunton, Edward Ford Building (A27) Fisher Road, University of Sydney, NSW 2006 Australia. Email: Jenny.Gunton@sydney.edu.au.
First published August 18, 2020 - More info
Hypoxia can be defined as a relative deficiency in the amount of oxygen reaching the tissues. Hypoxia-inducible factors (HIFs) are critical regulators of the mammalian response to hypoxia. In normal circumstances, HIF-1α protein turnover is rapid, and hyperglycemia further destabilizes the protein. In addition to their role in diabetes pathogenesis, HIFs are implicated in development of the microvascular and macrovascular complications of diabetes. Improving glucose control in people with diabetes increases HIF-1α protein and has wide-ranging benefits, some of which are at least partially mediated by HIF-1α. Nevertheless, most strategies to improve diabetes or its complications via regulation of HIF-1α have not currently proven to be clinically useful. The intersection of HIF biology with diabetes is a complex area in which many further questions remain, especially regarding the well-conducted studies clearly describing discrepant effects of different methods of increasing HIF-1α, even within the same tissues. This Review presents a brief overview of HIFs; discusses the range of evidence implicating HIFs in β cell dysfunction, diabetes pathogenesis, and diabetes complications; and examines the differing outcomes of HIF-targeting approaches in these conditions.
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