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A systems biology a...
A systems biology analysis connects insulin receptor signaling with glucose transporter translocation in rat adipocytes
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- Bergqvist, Niclas (author)
- Linköpings universitet,Linköping University,Institutionen för medicinsk teknik,Tekniska fakulteten
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- Nyman, Elin (author)
- Linköpings universitet,Linköping University,AstraZeneca RandD, Sweden,Avdelningen för medicinsk teknik,Tekniska fakulteten
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- Cedersund, Gunnar (author)
- Linköpings universitet,Linköping University,Avdelningen för medicinsk teknik,Tekniska fakulteten,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten
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- Stenkula, Karin G. (author)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups,Lund University, Sweden
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(creator_code:org_t)
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017
- 2017
- English 12 s.
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In: Journal of Biological Chemistry. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 1083-351X .- 0021-9258. ; 292:27, s. 11206-11217
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Abstract
Subject headings
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- Type 2 diabetes is characterized by insulin resistance, which arises from malfunctions in the intracellular insulin signaling network. Knowledge of the insulin signaling network is fragmented, and because of the complexity of this network, little consensus has emerged for the structure and importance of the different branches of the network. To help overcome this complexity, systems biology mathematical models have been generated for predicting both the activation of the insulin receptor (IR) and the redistribution of glucose transporter 4 (GLUT4) to the plasma membrane. Although the insulin signal transduction between IR and GLUT4 has been thoroughly studied with modeling and time-resolved data in human cells, comparable analyses in cells from commonly used model organisms such as rats and mice are lacking. Here, we combined existing data and models for rat adipocytes with new data collected for the signaling network between IR and GLUT4 to create a model also for their interconnections. To describe all data (>140 data points), the model needed three distinct pathways from IR to GLUT4: (i) via protein kinase B (PKB) and Akt substrate of 160 kDa (AS160), (ii) via an AS160-independent pathway from PKB, and (iii) via an additional pathway from IR, e.g. affecting the membrane constitution. The developed combined model could describe data not used for training the model and was used to generate predictions of the relative contributions of the pathways from IR to translocation of GLUT4. The combined model provides a systems-level understanding of insulin signaling in rat adipocytes, which, when combined with corresponding models for human adipocytes, may contribute to model-based drug development for diabetes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
Keyword
- adipocyte
- cell signaling
- glucose transporter type 4 (GLUT4)
- insulin
- insulin signaling
- mathematical modeling
- mechanistic modeling
Publication and Content Type
- art (subject category)
- ref (subject category)
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