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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

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Authors

Taliesin Pearson

JONATHAN WATTIS jonathan.wattis@nottingham.ac.uk
Professor of Applied Mathematics

JOHN KING JOHN.KING@NOTTINGHAM.AC.UK
Professor of Theoretical Mechanics

Ian McDonald

Dawn Mazzatti



Abstract

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

Journal Article Type Article
Acceptance Date Jun 3, 2016
Online Publication Date Jun 15, 2016
Deposit Date Jun 7, 2016
Publicly Available Date Jun 15, 2016
Journal Bulletin of Mathematical Biology
Print ISSN 0092-8240
Electronic ISSN 1522-9602
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 78
Issue 6
DOI https://doi.org/10.1007/s11538-016-0181-1
Public URL https://nottingham-repository.worktribe.com/output/795046
Publisher URL http://link.springer.com/article/10.1007/s11538-016-0181-1

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