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Topp2000_BetaCellMass_Diabetes


ABSTRACT: This model is from the article: A model of beta-cell mass, insulin, and glucose kinetics: pathways to diabetes. Topp B, Promislow K, deVries G, Miura RM, Finegood DT. J Theor Biol.2000 Oct 21;206(4):605-19. 11013117, Abstract: Diabetes is a disease of the glucose regulatory system that is associated with increased morbidity and early mortality. The primary variables of this system are beta-cell mass, plasma insulin concentrations, and plasma glucose concentrations. Existing mathematical models of glucose regulation incorporate only glucose and/or insulin dynamics. Here we develop a novel model of beta -cell mass, insulin, and glucose dynamics, which consists of a system of three nonlinear ordinary differential equations, where glucose and insulin dynamics are fast relative to beta-cell mass dynamics. For normal parameter values, the model has two stable fixed points (representing physiological and pathological steady states), separated on a slow manifold by a saddle point. Mild hyperglycemia leads to the growth of the beta -cell mass (negative feedback) while extreme hyperglycemia leads to the reduction of the beta-cell mass (positive feedback). The model predicts that there are three pathways in prolonged hyperglycemia: (1) the physiological fixed point can be shifted to a hyperglycemic level (regulated hyperglycemia), (2) the physiological and saddle points can be eliminated (bifurcation), and (3) progressive defects in glucose and/or insulin dynamics can drive glucose levels up at a rate faster than the adaptation of the beta -cell mass which can drive glucose levels down (dynamical hyperglycemia).

DISEASE(S): Diabetes Mellitus

SUBMITTER: Ishan Ajmera  

PROVIDER: BIOMD0000000341 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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Publications

A model of beta-cell mass, insulin, and glucose kinetics: pathways to diabetes.

Topp B B   Promislow K K   deVries G G   Miura R M RM   Finegood D T DT  

Journal of theoretical biology 20001001 4


Diabetes is a disease of the glucose regulatory system that is associated with increased morbidity and early mortality. The primary variables of this system are beta-cell mass, plasma insulin concentrations, and plasma glucose concentrations. Existing mathematical models of glucose regulation incorporate only glucose and/or insulin dynamics. Here we develop a novel model of beta -cell mass, insulin, and glucose dynamics, which consists of a system of three nonlinear ordinary differential equatio  ...[more]

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