Mathematical modeling and analysis of insulin clearance in vivo
Open accessAbstract
BACKGROUND: Analyzing the dynamics of insulin concentration in the blood is necessary for a comprehensive understanding of the effects of insulin in vivo. Insulin removal from the blood has been addressed in many studies. The results are highly variable with respect to insulin clearance and the relative contributions of hepatic and renal insulin degradation. RESULTS: We present a dynamic mathematical model of insulin concentration in the blood and of insulin receptor activation in hepatocytes. The model describes renal and hepatic insulin degradation, pancreatic insulin secretion and nonspecific insulin binding in the liver. Hepatic insulin receptor activation by insulin binding, receptor internalization and autophosphorylation is explicitly included in the model. We present a detailed mathematical analysis of insulin degradation and insulin clearance. Stationary model analysis shows that degradation rates, relative contributions of the different tissues to total insulin degradation and insulin clearance highly depend on the insulin concentration. CONCLUSION: This study provides a detailed dynamic model of insulin concentration in the blood and of insulin receptor activation in hepatocytes. Experimental data sets from literature are used for the model validation. We show that essential dynamic and stationary characteristics of insulin degradation are nonlinear and depend on the actual insulin concentration.
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At high insulin levels, the kidney is the main site of insulin degradation, more so than the liver.
“it has been reported that renal insulin degradation is predominant compared with liver at high insulin concentrations [40]”
From Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats (2015) · cites this paper as [40]
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References 62 · Cited by 35
- Authors
- Koschorreck, M., & Gilles, E. D.
- Affiliations
- Max Planck Institute for Dynamics of Complex Technical Systems (DE)
- Corresponding author
- Koschorreck, Markus
- Venue
- BMC Systems Biology
- Published
- 2008-05-13
- Volume
- 2
- Issue
- 1
- Pages
- 43-43
- ISSN
- 1752-0509 (ISSN-L)
- PMC
- PMC2430945
- OpenAlex
- W2157472563
- Cited by
- 35
- References
- 62
- Citations by year
- 2026: 2 · 2024: 1 · 2022: 1 · 2020: 3 · 2019: 1 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Systems Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Eberhard Karls Universität Tübingen
- Bundesministerium für Bildung und Forschung
- Universität Leipzig
- Universität Stuttgart
- Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin clearance, insulin degradation, insulin receptor activation, hepatocytes, insulin receptor internalization, autophosphorylation, pancreatic insulin secretion
- MeSH terms
- Insulin Secretion, Animals, Blood Glucose, Half-Life, Insulin, Kidney, Models, Biological, Pancreas, Phosphorylation, Receptor, Insulin, Protein Transport, Hepatocytes, Rats
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