Dynamical modeling the effect of glucagon-like peptide on glucose-insulin regulatory system based on mice experimental observation

Abstract

As an emerging global epidemic, type 2 diabetes mellitus (T2DM) represents one of the leading causes of morbidity and mortality worldwide. Existing evidences demonstrated that glucagon-like peptide-1 (GLP-1) modulate the glucose regulatory system by enhancing the β-cell function. However, the detailed process of GLP-1 in glycaemic regulator for T2DM remains to be clarified. Thus, in this study, we propose an Institute of Cancer Research (ICR) mice high fat and cholesterol dietary experimental data-driven mathematical model to investigate the secretory effect of GLP-1 on the dynamics of glucose-insulin regulatory system. Specifically, we develop a mathematical model of GLP-1 dynamics as part of the interaction model of β-cell, insulin, and glucose dynamics. The parameter estimation and data fitting are in agreement with the data in mice experiments In addition, uncertainty quantification is performed to explore the possible factors that influence the pathways leading to the pathological state. Model analyses reveal that the high fat or high cholesterol diet stimulated GLP-1 plays an important role in the dynamics of glucose, insulin and β cells in short-term. These results show that enhanced GLP-1 may mitigate the dysregulation of glucose-insulin regulatory system via promoting the β cells function and stimulating secretion of insulin, which offers an in-depth insights into the mechanistic of hyperglycemia from dynamical approach and provide the theoretical basis for GLP-1 served as a potential clinical targeted drug for treatment of T2DM.

Keywords: Diabetes; Dynamical model; Glucagon-like peptide-1; Glycaemic regulatory; Incretion effect.