The role of mitochondria in insulin resistance and type 2 diabetes mellitus

This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensit...

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Published in:Nature reviews. Endocrinology Vol. 8; no. 2; pp. 92 - 103
Main Authors: Szendroedi, Julia, Phielix, Esther, Roden, Michael
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.02.2012
Nature Publishing Group
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ISSN:1759-5029, 1759-5037, 1759-5037
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Abstract This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity. Type 2 diabetes mellitus (T2DM) has been related to alterations of oxidative metabolism in insulin-responsive tissues. Overt T2DM can present with acquired or inherited reductions of mitochondrial oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and plasticity of mitochondria and/or lower mitochondrial content in skeletal muscle cells and potentially also in hepatocytes. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as the result of blunted mitochondrial plasticity. Hereditary insulin resistance is frequently associated with reduced mitochondrial activity at rest, probably due to diminished mitochondrial content. Lifestyle and pharmacological interventions can enhance the capacity for oxidative phosphorylation and mitochondrial content and improve insulin resistance in some (pre)diabetic cases. Various mitochondrial features can be abnormal but are not necessarily responsible for all forms of insulin resistance. Nevertheless, mitochondrial abnormalities might accelerate progression of insulin resistance and subsequent organ dysfunction via increased production of reactive oxygen species. This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity. Key Points Overt type 2 diabetes mellitus is associated with reduced oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and mitochondrial plasticity in insulin-responsive tissues Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial plasticity that results in the inability of the organism to switch from fatty acid to glucose oxidation in skeletal muscle Hereditary insulin resistance can be linked to reduced resting mitochondrial activity at least partly due to a decreased mitochondrial content Lifestyle and pharmacological interventions can enhance oxidative phosphorylation capacity and mitochondrial content, and in most cases improve insulin resistance in (pre)diabetic states Reduced oxidative phosphorylation capacity is unlikely to be the general cause of all forms of insulin resistance but might accelerate its progression and subsequent organ dysfunction via increased production of reactive oxygen species
AbstractList Type 2 diabetes mellitus (T2DM) has been related to alterations of oxidative metabolism in insulin-responsive tissues. Overt T2DM can present with acquired or inherited reductions of mitochondrial oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and plasticity of mitochondria and/or lower mitochondrial content in skeletal muscle cells and potentially also in hepatocytes. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as the result of blunted mitochondrial plasticity. Hereditary insulin resistance is frequently associated with reduced mitochondrial activity at rest, probably due to diminished mitochondrial content. Lifestyle and pharmacological interventions can enhance the capacity for oxidative phosphorylation and mitochondrial content and improve insulin resistance in some (pre)diabetic cases. Various mitochondrial features can be abnormal but are not necessarily responsible for all forms of insulin resistance. Nevertheless, mitochondrial abnormalities might accelerate progression of insulin resistance and subsequent organ dysfunction via increased production of reactive oxygen species. This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity.
This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity. Type 2 diabetes mellitus (T2DM) has been related to alterations of oxidative metabolism in insulin-responsive tissues. Overt T2DM can present with acquired or inherited reductions of mitochondrial oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and plasticity of mitochondria and/or lower mitochondrial content in skeletal muscle cells and potentially also in hepatocytes. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as the result of blunted mitochondrial plasticity. Hereditary insulin resistance is frequently associated with reduced mitochondrial activity at rest, probably due to diminished mitochondrial content. Lifestyle and pharmacological interventions can enhance the capacity for oxidative phosphorylation and mitochondrial content and improve insulin resistance in some (pre)diabetic cases. Various mitochondrial features can be abnormal but are not necessarily responsible for all forms of insulin resistance. Nevertheless, mitochondrial abnormalities might accelerate progression of insulin resistance and subsequent organ dysfunction via increased production of reactive oxygen species. This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity. Key Points Overt type 2 diabetes mellitus is associated with reduced oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and mitochondrial plasticity in insulin-responsive tissues Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial plasticity that results in the inability of the organism to switch from fatty acid to glucose oxidation in skeletal muscle Hereditary insulin resistance can be linked to reduced resting mitochondrial activity at least partly due to a decreased mitochondrial content Lifestyle and pharmacological interventions can enhance oxidative phosphorylation capacity and mitochondrial content, and in most cases improve insulin resistance in (pre)diabetic states Reduced oxidative phosphorylation capacity is unlikely to be the general cause of all forms of insulin resistance but might accelerate its progression and subsequent organ dysfunction via increased production of reactive oxygen species
Type 2 diabetes mellitus (T2DM) has been related to alterations of oxidative metabolism in insulin-responsive tissues. Overt T2DM can present with acquired or inherited reductions of mitochondrial oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and plasticity of mitochondria and/or lower mitochondrial content in skeletal muscle cells and potentially also in hepatocytes. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as the result of blunted mitochondrial plasticity. Hereditary insulin resistance is frequently associated with reduced mitochondrial activity at rest, probably due to diminished mitochondrial content. Lifestyle and pharmacological interventions can enhance the capacity for oxidative phosphorylation and mitochondrial content and improve insulin resistance in some (pre)diabetic cases. Various mitochondrial features can be abnormal but are not necessarily responsible for all forms of insulin resistance. Nevertheless, mitochondrial abnormalities might accelerate progression of insulin resistance and subsequent organ dysfunction via increased production of reactive oxygen species. This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity. Szendroedi, J. et al. Nat. Rev. Endocrinol. 8, 92-103 (2012); published online 13 September 2011; doi: 10.1038/nrendo.2011.138
Type 2 diabetes mellitus (T2DM) has been related to alterations of oxidative metabolism in insulin-responsive tissues. Overt T2DM can present with acquired or inherited reductions of mitochondrial oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and plasticity of mitochondria and/or lower mitochondrial content in skeletal muscle cells and potentially also in hepatocytes. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as the result of blunted mitochondrial plasticity. Hereditary insulin resistance is frequently associated with reduced mitochondrial activity at rest, probably due to diminished mitochondrial content. Lifestyle and pharmacological interventions can enhance the capacity for oxidative phosphorylation and mitochondrial content and improve insulin resistance in some (pre)diabetic cases. Various mitochondrial features can be abnormal but are not necessarily responsible for all forms of insulin resistance. Nevertheless, mitochondrial abnormalities might accelerate progression of insulin resistance and subsequent organ dysfunction via increased production of reactive oxygen species. This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity.Type 2 diabetes mellitus (T2DM) has been related to alterations of oxidative metabolism in insulin-responsive tissues. Overt T2DM can present with acquired or inherited reductions of mitochondrial oxidative phosphorylation capacity, submaximal ADP-stimulated oxidative phosphorylation and plasticity of mitochondria and/or lower mitochondrial content in skeletal muscle cells and potentially also in hepatocytes. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as the result of blunted mitochondrial plasticity. Hereditary insulin resistance is frequently associated with reduced mitochondrial activity at rest, probably due to diminished mitochondrial content. Lifestyle and pharmacological interventions can enhance the capacity for oxidative phosphorylation and mitochondrial content and improve insulin resistance in some (pre)diabetic cases. Various mitochondrial features can be abnormal but are not necessarily responsible for all forms of insulin resistance. Nevertheless, mitochondrial abnormalities might accelerate progression of insulin resistance and subsequent organ dysfunction via increased production of reactive oxygen species. This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity.
Audience Academic
Author Phielix, Esther
Roden, Michael
Szendroedi, Julia
Author_xml – sequence: 1
  givenname: Julia
  surname: Szendroedi
  fullname: Szendroedi, Julia
  organization: Institute for Clinical Diabetology, German Diabetes Center, Department of Metabolic Diseases, University Clinics Düsseldorf, Heinrich-Heine University
– sequence: 2
  givenname: Esther
  surname: Phielix
  fullname: Phielix, Esther
  organization: Institute for Clinical Diabetology, German Diabetes Center
– sequence: 3
  givenname: Michael
  surname: Roden
  fullname: Roden, Michael
  email: michael.roden@ddz.uni-duesseldorf.de
  organization: Institute for Clinical Diabetology, German Diabetes Center, Department of Metabolic Diseases, University Clinics Düsseldorf, Heinrich-Heine University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/21912398$$D View this record in MEDLINE/PubMed
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18285554 - Diabetes. 2008 May;57(5):1166-75
17472434 - PLoS Med. 2007 May;4(5):e154
15894466 - Biochim Biophys Acta. 2005 Jun 30;1741(1-2):206-14
18325881 - Am J Physiol Endocrinol Metab. 2008 Mar;294(3):E640-2; author reply E643-4
12351431 - Diabetes. 2002 Oct;51(10):2944-50
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Snippet This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with...
Type 2 diabetes mellitus (T2DM) has been related to alterations of oxidative metabolism in insulin-responsive tissues. Overt T2DM can present with acquired or...
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SubjectTerms 631/443/319/333
631/80/86/2367
692/699/2743/137/773
Animals
Development and progression
Diabetes
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - physiopathology
Endocrinology
Fatty acids
Glucose
Humans
Hyperlipidemias - complications
Hyperlipidemias - metabolism
Hyperlipidemias - physiopathology
Insulin resistance
Insulin Resistance - physiology
Medicine
Medicine & Public Health
Metabolism
Metabolites
Mitochondria
Mitochondria, Muscle - physiology
Muscle, Skeletal - metabolism
Muscle, Skeletal - physiology
Musculoskeletal system
Oxidation
Oxidative Coupling
Oxidative Phosphorylation
Phosphorylation
Physiological aspects
review-article
Terminology
Type 2 diabetes
Title The role of mitochondria in insulin resistance and type 2 diabetes mellitus
URI https://link.springer.com/article/10.1038/nrendo.2011.138
https://www.ncbi.nlm.nih.gov/pubmed/21912398
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