Pathogenesis of diabetic complications: Exploring hypoxic niche formation and HIF-1α activation
Open accessAbstract
Hypoxia is a common feature of diabetic tissues, which highly correlates to the progression of diabetes. The formation of hypoxic context is induced by disrupted oxygen homeostasis that is predominantly driven by vascular remodeling in diabetes. While different types of vascular impairments have been reported, the specific features and underlying mechanisms are yet to be fully understood. Under hypoxic condition, cells upregulate hypoxia-inducible factor-1α (HIF-1α), an oxygen sensor that coordinates oxygen concentration and cell metabolism under hypoxic conditions. However, diabetic context exploits this machinery for pathogenic functions. Although HIF-1α protects cells from diabetic insult in multiple tissues, it also jeopardizes cell function in the retina. To gain a deeper understanding of hypoxia in diabetic complications, we focus on the formation of tissue hypoxia and the outcomes of HIF-1α dysregulation under diabetic context. Hopefully, this review can provide a better understanding on hypoxia biology in diabetes.
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Chronic hyperglycaemia is associated with heightened ROS levels from mitochondrial and cytosolic compartments, enabling HIF-1α accumulation by interfering with PHD activity through oxygen-independent mechanisms.
“Chronic hyperglycaemia is associated with is associated with heightened reactive oxygen species levels originating from mitochondrial and cytosolic compartment, which enables HIF-1α accumulation by interfering with prolyl hydroxylase activity through oxygen-independent mechanisms [[233], [234], [235]].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [235]
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HIF inhibition: Current strategies and clinical challenges
Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3 · see citing works
“Chronic hyperglycaemia is associated with is associated with heightened reactive oxygen species levels originating from mitochondrial and cytosolic compartment, which enables HIF-1 α accumulation by interfering with prolyl hydroxylase activity through oxygen-independent mechanisms [233 – 235].”
- Authors
- Bi, J., Zhou, W., & Tang, Z.
- Affiliations
- Southwest Medical University (CN)
- Baylor College of Medicine (US)
- Corresponding author
- Tang, Zonghao
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2024-03
- Volume
- 172
- Pages
- 116202
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4391627318
- Cited by
- 19
- References
- 10
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 5
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- diabetes complications, hypoxia, hypoxic niche, HIF-1α, hypoxia-inducible factor-1α, vascular remodeling, oxygen homeostasis, diabetic retinopathy, cellular metabolism
- MeSH terms
- Hypoxia, Diabetes Mellitus, Humans, Oxygen, Retina, Vascular Remodeling
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