The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
Open accessAbstract
Whilst the human body expends energy constantly, the human diet consists of a mix of carbohydrates and fats delivered in a discontinuous manner. To deal with this sporadic supply of energy, there are transport, storage and utilisation mechanisms, for both carbohydrates and fats, around all tissues of the body. Insulin-resistant states such as type 2 diabetes and obesity are characterised by reduced efficiency of these mechanisms. Exactly how these insulin-resistant states develop, for example whether there is an order in which tissues become insulin resistant, is an active area of research with the hope of gaining a better overall understanding of insulin resistance. In this paper, we use a previously derived system of 12 first-order coupled differential equations that describe the transport between, and storage in, different tissues of the human body. We briefly revisit the derivation of the model before parametrising the model to account for insulin resistance. We then solve the model numerically, separately simulating each individual tissue as insulin resistant, and discuss and compare these results, drawing three main conclusions. The implications of these results are in accordance with biological intuition. First, insulin resistance in a tissue creates a knock-on effect on the other tissues in the body, whereby they attempt to compensate for the reduced efficiency of the insulin-resistant tissue. Second, insulin resistance causes a fatty liver, and the insulin resistance of tissues other than the liver can cause fat to accumulate in the liver. Finally, although insulin resistance in individual tissues can cause slightly reduced skeletal muscle metabolic flexibility, it is when the whole body is insulin resistant that the biggest effect on skeletal muscle flexibility is seen.
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Insulin resistance of individual tissues causes slightly reduced skeletal muscle metabolic flexibility.
“slightly reduced skeletal muscle metabolic flexibility is caused by insulin resistance of individual tissues”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [312]
The same compartmentalized mathematical model simulated that insulin resistance causes fatty liver regardless of the site of insulin resistance in the body.
“The model also simulated that insulin resistance causes fatty liver regardless of the site of insulin resistance in the body”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [312]
A compartmentalized mathematical model of human metabolism (not based on Recon 2) suggested that insulin resistance in one tissue creates a knock-on effect in other tissues that tries to compensate for reduced flexibility.
“suggested that insulin resistance in one tissue created a knock-on effect in other tissues that tries to compensate for the reduced flexibility”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [312]
The strongest effect on muscle metabolic flexibility is observed when the whole body is insulin resistant.
“the strongest effect on muscle metabolic flexibility is observed when the whole body is insulin resistant”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [312]
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Cited by
Sorted by citations
Pathophysiology of type 2 diabetes mellitus
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- Authors
- Pearson, T., Wattis, J. A. D., King, J. R., MacDonald, I. A., & Mazzatti, D. J.
- Affiliations
- University of Nottingham (GB)
- Unilever (United States) (US)
- Corresponding author
- Wattis, Jonathan A. D.
- Venue
- Bulletin of Mathematical Biology
- Published
- 2016-06
- Volume
- 78
- Issue
- 6
- Pages
- 1189-1217
- ISSN
- 0092-8240 (ISSN-L)
- 1522-9602
- PMC
- PMC4949305
- OpenAlex
- W2416477374
- Cited by
- 37
- References
- 22
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 4
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Bulletin of Mathematical Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
- Funders
- University of Nottingham
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- insulin resistance, type 2 diabetes, obesity, hepatic steatosis, systems of differential equations
- MeSH terms
- Adipose Tissue, Computer Simulation, Diabetes Mellitus, Type 2, Energy Metabolism, Glucose, Humans, Insulin Resistance, Liver, Models, Biological, Obesity, Tissue Distribution, Muscle, Skeletal, Lipid Metabolism, Metabolic Networks and Pathways, Mathematical Concepts
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