Objective:A computational model of insulin secretion and glucose metabolism for assisting the diagnosis of diabetes mellitus in clinical research is introduced.The proposed method for the estimation of parameters for...Objective:A computational model of insulin secretion and glucose metabolism for assisting the diagnosis of diabetes mellitus in clinical research is introduced.The proposed method for the estimation of parameters for a system of ordinary differential equations(ODEs)that represent the time course of plasma glucose and insulin concentrations during glucose tolerance test(GTT)in physiological studies is presented.The aim of this study was to explore how to interpret those laboratory glucose and insulin data as well as enhance the Ackerman mathematical model.Methods:Parameters estimation for a system of ODEs was performed by minimizing the sum of squared residuals(SSR)function,which quantifies the difference between theoretical model predictions and GTT's experimental observations.Our proposed perturbation search and multiple-shooting methods were applied during the estimating process.Results:Based on the Ackerman's published data,we estimated the key parameters by applying R-based iterative computer programs.As a result,the theoretically simulated curves perfectly matched the experimental data points.Our model showed that the estimated parameters,computed frequency and period values,were proven a good indicator of diabetes.Conclusion:The present paper introduces a computational algorithm to biomedical problems,particularly to endocrinology and metabolism fields,which involves two coupled differential equations with four parameters describing the glucose-insulin regulatory system that Ackerman proposed earlier.The enhanced approach may provide clinicians in endocrinology and metabolism field insight into the transition nature of human metabolic mechanism from normal to impaired glucose tolerance.展开更多
It was estimated that every year more than 30000 persons in the United States- approximately 80 people per day- are diagnosed with type 1 diabetes(T1D). T1 D is caused by autoimmune destruction of the pancreatic islet...It was estimated that every year more than 30000 persons in the United States- approximately 80 people per day- are diagnosed with type 1 diabetes(T1D). T1 D is caused by autoimmune destruction of the pancreatic islet(β cells) cells. Islet transplantation has become a promising therapy option for T1 D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography(PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism. The successful PET imaging of islets would be able to localize the specific site where transplanted islets engraft in the liver, and to quantify the level of islets remain alive and functional over time. This information would be vital to establishing and evaluating the efficiency of pancreatic islet transplantation. Many novel imaging agents have been developed to improve the sensitivity and specificity of PET islet imaging. In this article, we summarize the latest developments in carbon-11, fluorine-18, copper-64, and gallium-68 labeled radioligands for the PET imaging of pancreatic islet cells.展开更多
基金supported by a grant from the NIH(No.U42 RR16607)
文摘Objective:A computational model of insulin secretion and glucose metabolism for assisting the diagnosis of diabetes mellitus in clinical research is introduced.The proposed method for the estimation of parameters for a system of ordinary differential equations(ODEs)that represent the time course of plasma glucose and insulin concentrations during glucose tolerance test(GTT)in physiological studies is presented.The aim of this study was to explore how to interpret those laboratory glucose and insulin data as well as enhance the Ackerman mathematical model.Methods:Parameters estimation for a system of ODEs was performed by minimizing the sum of squared residuals(SSR)function,which quantifies the difference between theoretical model predictions and GTT's experimental observations.Our proposed perturbation search and multiple-shooting methods were applied during the estimating process.Results:Based on the Ackerman's published data,we estimated the key parameters by applying R-based iterative computer programs.As a result,the theoretically simulated curves perfectly matched the experimental data points.Our model showed that the estimated parameters,computed frequency and period values,were proven a good indicator of diabetes.Conclusion:The present paper introduces a computational algorithm to biomedical problems,particularly to endocrinology and metabolism fields,which involves two coupled differential equations with four parameters describing the glucose-insulin regulatory system that Ackerman proposed earlier.The enhanced approach may provide clinicians in endocrinology and metabolism field insight into the transition nature of human metabolic mechanism from normal to impaired glucose tolerance.
基金Supported by The grant from the Larry L.Hillblom Foundation
文摘It was estimated that every year more than 30000 persons in the United States- approximately 80 people per day- are diagnosed with type 1 diabetes(T1D). T1 D is caused by autoimmune destruction of the pancreatic islet(β cells) cells. Islet transplantation has become a promising therapy option for T1 D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography(PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism. The successful PET imaging of islets would be able to localize the specific site where transplanted islets engraft in the liver, and to quantify the level of islets remain alive and functional over time. This information would be vital to establishing and evaluating the efficiency of pancreatic islet transplantation. Many novel imaging agents have been developed to improve the sensitivity and specificity of PET islet imaging. In this article, we summarize the latest developments in carbon-11, fluorine-18, copper-64, and gallium-68 labeled radioligands for the PET imaging of pancreatic islet cells.