Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia
Abstract
Type 2 diabetes (T2D) is a complex multifactorial disease that emerges from the combination of genetic and environmental factors, and obesity, lifestyle, and aging are the most relevant risk factors. Hyperglycemia is the main metabolic feature of T2D as a consequence of insulin resistance and β-cell dysfunction. Among the cellular alterations induced by hyperglycemia, the overproduction of reactive oxygen species (ROS) and consequently oxidative stress, accompanied by a reduced antioxidant response and impaired DNA repair pathways, represent essential mechanisms underlying the pathophysiology of T2D and the development of late complications. Mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation are also closely correlated with insulin resistance and β-cell dysfunction. This review focus on the mechanisms by which oxidative stress, mitochondrial dysfunction, ER stress, and inflammation are involved in the pathophysiology of T2D, highlighting the importance of the antioxidant response and DNA repair mechanisms counteracting the development of the disease. Moreover, we indicate evidence on how nutritional interventions effectively improve diabetes care. Additionally, we address key molecular characteristics and signaling pathways shared between T2D and Alzheimer's disease (AD), which might probably be implicated in the risk of T2D patients to develop AD.
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- Authors
- Lima, J. E. B. F., Moreira, N. C. S., & Sakamoto-Hojo, E. T.
- Venue
- Mutation Research/Genetic Toxicology and Environmental Mutagenesis
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 874-875
- Pages
- 503437
- ISSN
- 1383-5718 (ISSN-L)
- OpenAlex
- W4200140669
- Cited by
- 203
- References
- 212
- Citations by year
- 2026: 42 · 2025: 72 · 2024: 44 · 2023: 30 · 2022: 15
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Mutation Research/Genetic Toxicology and Environmental Mutagenesis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (142223/2019-0, 309854/2017-2)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 2 diabetes, pathophysiology, oxidative stress, reactive oxygen species, insulin resistance, beta-cell dysfunction, hyperglycemia, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, antioxidant response, DNA repair, obesity, diabetes risk factors, dietary intervention, Alzheimer's disease
- MeSH terms
- Antioxidants, Diabetes Mellitus, Type 2, Humans, Hyperglycemia, Inflammation, Insulin Resistance, Risk Factors, Oxidative Stress
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