Cited by 167Cancer, Hypoxia, and MetabolismDiabetes Management and ResearchPancreatic function and diabetes

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Hypoxia-inducible factors and diabetes

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Gunton, Jenny E.·2020·Journal of Clinical Investigation

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Abstract

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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Authors: Gunton, J. E.
Affiliations: The University of Sydney (AU)
Corresponding author: Gunton, Jenny E.
ORCID: Gunton, Jenny E.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2020-09-14
Volume: 130
Issue: 10
Pages: 5063-5073
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci137556
PMC: PMC7524477
OpenAlex: W3071274483
Cited by: 159
References: 163
Citations by year: 2026: 22 · 2025: 24 · 2024: 25 · 2023: 40 · 2022: 33 · 2021: 15
FWCI: 2.40
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: NHMRC (AppID1149976)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: hypoxia-inducible factor, HIF-1α, diabetes pathogenesis, hypoxia, hyperglycemia, beta-cell dysfunction, diabetes complications, microvascular complications, macrovascular complications, glycemic control
MeSH terms: Endothelial PAS Domain-Containing Protein 1, Animals, Diabetes Mellitus, Glucose, Humans, Models, Biological, Tissue Distribution, Diabetes Complications, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit

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