Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
Abstract
Nearly unlimited supplies of energy-dense foods and technologies that encourage sedentary behaviour have introduced a new threat to the survival of our species: obesity and its co-morbidities. Foremost among the co-morbidities is type 2 diabetes, which is projected to afflict 300 million people worldwide by 2020. Compliance with lifestyle modifications such as reduced caloric intake and increased physical activity has proved to be difficult for the general population, meaning that pharmacological intervention may be the only recourse for some. This epidemiological reality heightens the urgency for gaining a deeper understanding of the processes that cause metabolic failure of key tissues and organ systems in type 2 diabetes, as reviewed here.
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Enhanced fat metabolism with high-fat feeding leads to high levels of β-oxidation products that alter mitochondria and restrict ability to switch to glucose oxidation.
“More recent metabolomic studies now suggest that enhanced fat metabolism seen with high-fat feeding leads to high levels of β-oxidation products that alter mitochondria in a way that restrict the ability to switch to glucose oxidation (228).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [228]
Metabolic inflexibility, particularly impaired capacity to switch between fatty acid and glucose oxidation, has a pathogenic role in insulin resistance in type 2 diabetes and obesity.
“Moreover, the importance of fuel selectivity is underscored by studies indicating that “metabolic inflexibility” or impaired capacity to switch between nutrient utilization, in particular between fatty acid and glucose oxidation, has a pathogenic role in the insulin resistance commonly seen in type 2 diabetes and obesity (228).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [228]
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- Authors
- Muoio, D. M., & Newgard, C. B.
- Affiliations
- Duke University (US)
- Corresponding author
- Newgard, Christopher B.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2008-03
- Volume
- 9
- Issue
- 3
- Pages
- 193-205
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W1657478053
- Cited by
- 1,177
- References
- 135
- Citations by year
- 2026: 31 · 2025: 33 · 2024: 49 · 2023: 66 · 2022: 51 · 2021: 59 · 2020: 62 · 2019: 67 · 2018: 65 · 2017: 74 · 2016: 77 · 2015: 81 · 2014: 83 · 2013: 64 · 2012: 75
- FWCI
- 13.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 2 diabetes, insulin resistance, beta-cell failure, pancreatic beta cells, obesity, metabolic failure, molecular mechanisms, pharmacological interventions
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Glucose, Humans, Insulin, Insulin Resistance, Signal Transduction, Insulin-Secreting Cells
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