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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)

Blood 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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How the glucose regulation system fails?

- pathological conditions Meal uptake

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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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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

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.

Mathematical modeling of glucose regulation system

Equation A

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

System

Glucose regulation system can

be described by mathematical
model
Variables:
observable diagnosis test data (ex.
PG, insulin)

Equation B

Models/Equations:
Relations between variables based
on biological knowledge

Parameters:
parameter to be interpreted as
functionality of organ/component
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Oral glucose tolerance test (OGTT)

Plasma Glucose
Insulin

DM

Plasma Glucose
Insulin response

Normal

Glucose uptake

impulse

Time
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Estimation of individual organ function

= parameter estimation of model

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Plasma Glucose
Insulin

DM

Mathematical model of
glucose regulation system
With
Individual parameters

Parameter estimation
Insulin secretion: sec
Insulin sensitivity: sens

Drug selection
Lifestyle guidance
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What is issue in this area?

More precise model gives more biologically relevant

parameters

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Recent incites in glucose regulation system

- involvement of incretin -

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Incretin:
Is hormones released
from gut.
incretin

Promotes insulin release

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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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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