Hypoxia and hypoxia-inducible factors in diabetes and its complications

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 funct...

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Vydáno v:	Diabetologia Ročník 64; číslo 4; s. 709 - 716
Hlavní autoři:	Catrina, Sergiu-Bogdan, Zheng, Xiaowei
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2021 Springer Nature B.V
Témata:	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 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
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Abstract	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
AbstractList	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. 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 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.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.
Author	Zheng, Xiaowei Catrina, Sergiu-Bogdan
Author_xml	– sequence: 1 givenname: Sergiu-Bogdan orcidid: 0000-0002-6914-3902 surname: Catrina fullname: Catrina, Sergiu-Bogdan email: Sergiu-Bogdan.Catrina@ki.se organization: Department of Molecular Medicine and Surgery, Karolinska Institutet, Department of Endocrinology and Diabetes, Karolinska University Hospital, Center for Diabetes, Academic Specialist Centrum – sequence: 2 givenname: Xiaowei orcidid: 0000-0002-2648-1119 surname: Zheng fullname: Zheng, Xiaowei email: Xiaowei.zheng@ki.se organization: Department of Molecular Medicine and Surgery, Karolinska Institutet
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/33496820$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:145758245$$DView record from Swedish Publication Index (Karolinska Institutet)
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Issue	4
Keywords	Diabetic retinopathy Prolyl hydroxylase inhibitor Diabetes complications Hypoxia-inducible factor Diabetic nephropathy Hypoxia Insulin resistance Diabetes Review Diabetic foot ulcer
Language	English
License	Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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PublicationDate	2021-04-01
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PublicationPlace	Berlin/Heidelberg
PublicationPlace_xml	– name: Berlin/Heidelberg – name: Germany – name: Heidelberg
PublicationSubtitle	Clinical, Translational and Experimental Diabetes and Metabolism
PublicationTitle	Diabetologia
PublicationTitleAbbrev	Diabetologia
PublicationTitleAlternate	Diabetologia
PublicationYear	2021
Publisher	Springer Berlin Heidelberg Springer Nature B.V
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SubjectTerms	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 Medicine Medicine & Public Health Metabolic Diseases Molecular Targeted Therapy Oxygen - metabolism Prolyl-Hydroxylase Inhibitors - therapeutic use Repressor Proteins - metabolism Review Signal Transduction
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Title	Hypoxia and hypoxia-inducible factors in diabetes and its complications
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