Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress

Rolo, Anabela P.; Palmeira, Carlos M.

doi:10.1016/j.taap.2006.01.003

Cited by 1,007Mitochondrial Function and PathologyMetabolism, Diabetes, and CancerAdvanced Glycation End Products research

Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress

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Rolo, Anabela P., Palmeira, Carlos M.·2006·Toxicology and Applied Pharmacology

DOI 10.1016/j.taap.2006.01.003

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Abstract

Hyperglycemia resulting from uncontrolled glucose regulation is widely recognized as the causal link between diabetes and diabetic complications. Four major molecular mechanisms have been implicated in hyperglycemia-induced tissue damage: activation of protein kinase C (PKC) isoforms via de novo synthesis of the lipid second messenger diacylglycerol (DAG), increased hexosamine pathway flux, increased advanced glycation end product (AGE) formation, and increased polyol pathway flux. Hyperglycemia-induced overproduction of superoxide is the causal link between high glucose and the pathways responsible for hyperglycemic damage. In fact, diabetes is typically accompanied by increased production of free radicals and/or impaired antioxidant defense capabilities, indicating a central contribution for reactive oxygen species (ROS) in the onset, progression, and pathological consequences of diabetes. Besides oxidative stress, a growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. Mutations in mitochondrial DNA (mtDNA) and decreases in mtDNA copy number have been linked to the pathogenesis of type 2 diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters, glucose-stimulated insulin secretion, and nuclear-encoded uncoupling proteins (UCPs) in beta-cell glucose toxicity. This review focuses on a range of mitochondrial factors important in the pathogenesis of diabetes. We review the published literature regarding the direct effects of hyperglycemia on mitochondrial function and suggest the possibility of regulation of mitochondrial function at a transcriptional level in response to hyperglycemia. The main goal of this review is to include a fresh consideration of pathways involved in hyperglycemia-induced diabetic complications.

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Studies assessing mitochondrial copy number in skeletal muscle in insulin-resistant individuals have reported conflicting results.
“Thus, studies which have assessed mitochondrial copy number in skeletal muscle in insulin-resistant individuals have reported conflicting results [114–116].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [114]

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Authors: Rolo, A. P., & Palmeira, C. M.
Affiliations: Centro de Neurociências e Biologia Celular (PT)
Corresponding author: Palmeira, Carlos M.
ORCID: Rolo, Anabela P.
Palmeira, Carlos M.
Venue: Toxicology and Applied Pharmacology
Publisher: Elsevier BV
Published: 2006-04
Volume: 212
Issue: 2
Pages: 167-178
ISSN: 0041-008X (ISSN-L)
DOI: 10.1016/j.taap.2006.01.003
OpenAlex: W1966621383
Cited by: 1,007
References: 115
Citations by year: 2026: 21 · 2025: 35 · 2024: 43 · 2023: 36 · 2022: 42 · 2021: 58 · 2020: 57 · 2019: 44 · 2018: 65 · 2017: 48 · 2016: 59 · 2015: 70 · 2014: 65 · 2013: 64 · 2012: 60
FWCI: 3.24
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Toxicology and Applied Pharmacology (publishedVersion)
PubMed (publishedVersion)
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Keywords: diabetes mellitus, hyperglycemia, mitochondrial function, oxidative stress, type 2 diabetes, protein kinase C, diacylglycerol, hexosamine biosynthetic pathway, advanced glycation end products, polyol pathway, superoxide, reactive oxygen species, mitochondrial DNA mutations, mitochondrial DNA copy number, glucose transporters, glucose-stimulated insulin secretion, uncoupling proteins, diabetes complications
MeSH terms: Animals, Diabetes Mellitus, Gene Expression Regulation, Glucose, Humans, Hyperglycemia, Hypoglycemic Agents, Insulin, Mitochondria, Uncoupling Agents, Oxidative Stress, Insulin-Secreting Cells

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Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress

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