Chapter Hyperglycemia-Induced Endothelial Dysfunction

Glucose-induced endothelial dysfunction plays a fundamental role in the development of diabetic vascular complications and glycemic control (the foundation of diabetes care) provides limited protection against the cardiovascular complications. Therefore, identification of novel drug targets and trea...

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Hovedforfatter: Gero, Domokos
Format: Online
Sprog:engelsk
Udgivet: InTechOpen 2021
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Online adgang:ONIX_20210602_10.5772/intechopen.71433_371
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author Gero, Domokos
author_browse Gero, Domokos
author_facet Gero, Domokos
author_sort Gero, Domokos
collection Directory of Open Access Books
description Glucose-induced endothelial dysfunction plays a fundamental role in the development of diabetic vascular complications and glycemic control (the foundation of diabetes care) provides limited protection against the cardiovascular complications. Therefore, identification of novel drug targets and treatment approaches for diabetes complications represent a key direction of current pharmaceutical research. The “unifying theory” of hyperglycemia-induced endothelial cell injury organizes the events of cellular dysfunction in a linear cascade and identifies mitochondrial superoxide generation as the triggering event of the injury. Exposure to high glucose concentration for long periods or repeated glycemic swings may induce changes in metabolic substrate availability and lead to mitochondrial hyperpolarization. Changes in the mitochondrial membrane potential induce superoxide production by the electron transport chain and result in oxidative stress. Mitochondrial superoxide is also responsible for the induction of other sources of reactive oxygen species (ROS) within the cells, including advanced glycation end products (AGEs) and the NADPH oxidase. Mitochondria also show morphological changes and impaired assembly of the respiratory complexes occurs, which results in cellular energy failure, cell senescence and vascular dysfunction. Current intervention strategies aim to inhibit the mitochondrial ROS production and novel therapeutic approaches are expected to provide valuable tools in diabetes therapy in the upcoming years.
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spelling doab-20.500.12854ir-702722025-01-15T19:33:10Z Chapter Hyperglycemia-Induced Endothelial Dysfunction Gero, Domokos hyperglycemia, diabetes, endothelial cells, oxidative stress, mitochondria, electron transport chain, superoxide, bioenergetics thema EDItEUR::M Medicine and Nursing::MJ Clinical and internal medicine::MJD Cardiovascular medicine Glucose-induced endothelial dysfunction plays a fundamental role in the development of diabetic vascular complications and glycemic control (the foundation of diabetes care) provides limited protection against the cardiovascular complications. Therefore, identification of novel drug targets and treatment approaches for diabetes complications represent a key direction of current pharmaceutical research. The “unifying theory” of hyperglycemia-induced endothelial cell injury organizes the events of cellular dysfunction in a linear cascade and identifies mitochondrial superoxide generation as the triggering event of the injury. Exposure to high glucose concentration for long periods or repeated glycemic swings may induce changes in metabolic substrate availability and lead to mitochondrial hyperpolarization. Changes in the mitochondrial membrane potential induce superoxide production by the electron transport chain and result in oxidative stress. Mitochondrial superoxide is also responsible for the induction of other sources of reactive oxygen species (ROS) within the cells, including advanced glycation end products (AGEs) and the NADPH oxidase. Mitochondria also show morphological changes and impaired assembly of the respiratory complexes occurs, which results in cellular energy failure, cell senescence and vascular dysfunction. Current intervention strategies aim to inhibit the mitochondrial ROS production and novel therapeutic approaches are expected to provide valuable tools in diabetes therapy in the upcoming years. 2021-02-10T12:58:18Z 2021-06-02T10:10:43Z 2018 chapter ONIX_20210602_10.5772/intechopen.71433_371 https://library.oapen.org/handle/20.500.12657/49257 https://directory.doabooks.org/handle/20.500.12854/70272 eng open access image/jpeg image/jpeg image/jpeg n/a n/a n/a https://library.oapen.org/bitstream/20.500.12657/49257/1/57915.pdf https://library.oapen.org/bitstream/20.500.12657/49257/1/57915.pdf https://library.oapen.org/bitstream/20.500.12657/49257/1/57915.pdf InTechOpen 10.5772/intechopen.71433 10.5772/intechopen.71433 035ecc65-6737-43cf-a13a-6bdf67ce01f4 open access
spellingShingle hyperglycemia, diabetes, endothelial cells, oxidative stress, mitochondria, electron transport chain, superoxide, bioenergetics
thema EDItEUR::M Medicine and Nursing::MJ Clinical and internal medicine::MJD Cardiovascular medicine
Gero, Domokos
Chapter Hyperglycemia-Induced Endothelial Dysfunction
title Chapter Hyperglycemia-Induced Endothelial Dysfunction
title_full Chapter Hyperglycemia-Induced Endothelial Dysfunction
title_fullStr Chapter Hyperglycemia-Induced Endothelial Dysfunction
title_full_unstemmed Chapter Hyperglycemia-Induced Endothelial Dysfunction
title_short Chapter Hyperglycemia-Induced Endothelial Dysfunction
title_sort chapter hyperglycemia induced endothelial dysfunction
topic hyperglycemia, diabetes, endothelial cells, oxidative stress, mitochondria, electron transport chain, superoxide, bioenergetics
thema EDItEUR::M Medicine and Nursing::MJ Clinical and internal medicine::MJD Cardiovascular medicine
topic_facet hyperglycemia, diabetes, endothelial cells, oxidative stress, mitochondria, electron transport chain, superoxide, bioenergetics
thema EDItEUR::M Medicine and Nursing::MJ Clinical and internal medicine::MJD Cardiovascular medicine
url ONIX_20210602_10.5772/intechopen.71433_371
work_keys_str_mv AT gerodomokos chapterhyperglycemiainducedendothelialdysfunction