The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans

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 o...

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Main Authors: Pearson, Taliesin, Wattis, Jonathan A.D., King, John, McDonald, Ian, Mazzatti, Dawn
Format: Article
Published: Springer 2016
Online Access:https://eprints.nottingham.ac.uk/33792/
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author Pearson, Taliesin
Wattis, Jonathan A.D.
King, John
McDonald, Ian
Mazzatti, Dawn
author_facet Pearson, Taliesin
Wattis, Jonathan A.D.
King, John
McDonald, Ian
Mazzatti, Dawn
author_sort Pearson, Taliesin
building Nottingham Research Data Repository
collection Online Access
description 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-or der 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. Secondly, 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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spelling nottingham-337922020-05-04T17:56:34Z https://eprints.nottingham.ac.uk/33792/ The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans Pearson, Taliesin Wattis, Jonathan A.D. King, John McDonald, Ian Mazzatti, Dawn 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-or der 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. Secondly, 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 Springer 2016-06-15 Article PeerReviewed Pearson, Taliesin, Wattis, Jonathan A.D., King, John, McDonald, Ian and Mazzatti, Dawn (2016) The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans. Bulletin of Mathematical Biology, 78 (6). pp. 1189-1217. ISSN 1522-9602 http://link.springer.com/article/10.1007/s11538-016-0181-1 doi:10.1007/s11538-016-0181-1 doi:10.1007/s11538-016-0181-1
spellingShingle Pearson, Taliesin
Wattis, Jonathan A.D.
King, John
McDonald, Ian
Mazzatti, Dawn
The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
title The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
title_full The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
title_fullStr The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
title_full_unstemmed The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
title_short The effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
title_sort effects of insulin resistance on individual tissues: an application of a mathematical model of metabolism in humans
url https://eprints.nottingham.ac.uk/33792/
https://eprints.nottingham.ac.uk/33792/
https://eprints.nottingham.ac.uk/33792/