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Validation of the in vitro incubation of extensor digitorum longus muscle from mice with a mathematical model
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- Sögård, Peter (author)
- Högskolan i Skövde,Forskningscentrum för Systembiologi,Institutionen för vård och natur,Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden
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- Harlén, Mikael (author)
- Högskolan i Skövde,Institutionen för vård och natur
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- Long, Yun Chau (author)
- Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden
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- World Scientific, 2010
- 2010
- English.
- In: Journal of biological systems. - : World Scientific. - 0218-3390. ; 18:3, s. 687-707
- Journal article (peer-reviewed)
Abstract
Subject headings
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- In vitro incubation of tissues; in particular, skeletal muscles from rodents, is a widely-used experimental method in diabetes research. This experimental method has previously been validated, both experimentally and theoretically. However, much of the method's experimental data remains unclear, including the high-rate of lactate production and the lack of an observable increase in glycogen content, within a given time. The predominant hypothesis explaining the high-rate of lactate production is that this phenomenon is dependent on a mechanism in glycolysis that works as a safety valve, producing lactate when glucose uptake is super-physiological. Another hypothesis is that existing anoxia forces more ATP to be produced from glycolysis, leading to an increased lactate concentration. The lack of an observable increase in glycogen content is assumed to be dependent on limitations in sensitivity of the measuring method used. We derived a mathematical model to investigate which of these hypotheses is most likely to be correct. Using our model, data analysis indicates that the in vitro incubated muscle specimens, most likely are sensing the presence of existing anoxia, rather than an overflow in glycolysis. The anoxic milieu causes the high lactate production. The model also predicts an increased glycogenolysis. After mathematical analyses, an estimation of the glycogen concentration could be made with a reduced model. In conclusion, central anoxia is likely to cause spatial differences in glycogen concentrations throughout the entire muscle. Thus, data regarding total glycogen levels in the incubated muscle do not accurately represent the entire organ. The presented model allows for an estimation of total glycogen, despite spatial differences present in the muscle specimen.
Keyword
- Average
- Glycogen
- In Vitro
- Incubation
- Skeletal Muscle
- Naturvetenskap
- Natural sciences
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Sögård, Peter
- Harlén, Mikael
- Long, Yun Chau
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