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Mathematical modeling of glucose regulation system for diagnosis of diabetes

2015/5/26

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Human consists from multiple organs

Each organs exert their each function to keep human life

Some disease are caused by functionally-impaired/unregulated organs

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Sugar (Glucose)

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confidentialBlood glucose regulation system- glucose homeostasis -

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Glucose concentration is kept in constant by multiple organs functions

Hormones from pancreas plays key roles in blood glucose regulation. Insulin: decrease plasma

glucose Glucagon: increase plasma

glucose

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Diabetes mellitus (Diabetes, DM, ) Symptoms:

High plasma glucose concentration High urine glucose concentration

Complications caused by DM: chronic renal failure hardened arteries neurological disorder Etc.

Two groups Type I DM (childhood DM) Type II DM

Associated with bad lifestyle genetic backgrounds

Plasma glucose should be controlled to prevent DM associated complications

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confidentialHow the glucose regulation system fails?- pathological conditions -

Though the representative condition of DM is just high plasma glucose, DM have multiple pathological conditions. Impaired functionality of

pancreas

Decrease in insulin sensitivity of liver/tissue cells

Others

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Meal uptake

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Treatment options for DM

Representative mode of action of (conventional) DM drugs Enhancement of insulin

secretion

Enhancement of insulin sensitivity

Direct infusion of insulin

Lower glucose uptake

The drugs suitable for individual patients should be prescribed

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Evaluation of functionality of organs is required for appropriate treatment of DM

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How to know the functionality of organs?

Evaluation by biological assay with partially resected organ whole organ

Invasive / Impossible

We needs less/non-invasive method for functional evaluation of organs.

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Mathematical modeling of glucose regulation system

Glucose regulation system can be described by mathematical model

Variables: observable diagnosis test data (ex.

PG, insulin)

Models/Equations: Relations between variables based

on biological knowledge

Parameters: parameter to be interpreted as

functionality of organ/component9

Systemd ins(t)/dt = panc Glu(t)

Equation B

Equation A

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Oral glucose tolerance test (OGTT)

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Plasma GlucoseInsulin

DM

Plasma GlucoseInsulin

Normal

Glucose uptake

impulse

response

Time

confidentialEstimation of individual organ function= parameter estimation of model

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Plasma GlucoseInsulin

DMMathematical model of

glucose regulation systemWith

Individual parameters

Insulin secretion: secInsulin sensitivity: sens

Parameter estimation

Drug selectionLifestyle guidance

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What is issue in this area?

More precise model gives more biologically relevant parameters

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confidentialRecent incites in glucose regulation system- involvement of incretin -

Incretin: Is hormones released

from gut. GIP

GLP-1

Enhances insulin secretion from pancreas.

Is secreted when meal stimulate gut.

Some drugs targeting incretin were launched recently.

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incretin

Promotes insulin release

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Purpose of our project

Include incretin actions in mathematical model of glucose regulation system

It allows to estimates more biologically relevant parameters including (parameters related to incretin actions)

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