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A closed-loop multi-level model of glucose homeostasis.
Cansu Uluseker1, Giulia Simoni1, Luca Marchetti1
1The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI), Rovereto (TN), Italy.
Plos One
|February 9, 2018
Summary
This study introduces a multi-level, closed-loop model for glucose homeostasis, integrating cellular insulin signaling. The model accurately simulates glucose metabolism in normal and type 2 diabetes conditions.
Area of Science:
- Physiology
- Computational Biology
- Endocrinology
Background:
- Glucose homeostasis regulation is complex at cellular and systemic levels.
- Existing models often lack structured, multi-level descriptions of glucose metabolism.
- Type 2 diabetes presents significant challenges in understanding glucose regulation.
Purpose of the Study:
- To propose a multi-level, closed-loop model of whole-body glucose homeostasis.
- To integrate molecular details of insulin signaling in adipocytes.
- To simulate glucose metabolism under normal and type 2 diabetes conditions.
Main Methods:
- Developed a hierarchical model using ordinary differential equations.
- Simulated interactions between gut, liver, muscle, and adipose tissue.
- Incorporated a detailed model of insulin signaling cascade in adipocytes.
Main Results:
- The model provides a dynamic description of glucose and key regulatory hormones.
- Simulations represent an in silico subject adjusting to metabolic states.
- The model captures cellular-level insulin signaling variations.
Conclusions:
- The multi-level, closed-loop approach effectively describes glucose homeostasis determinants.
- The model architecture allows for future expansion with additional biological components.
- This approach offers a framework for studying complex metabolic diseases.
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