Bangladesh University of Engineering and Technology

Department of Biomedical Engineering

Physiological Control Systems Sessional

(BME 306)

Title: Dynamics of Glucose-Insulin Regulation

Experiment No.: 07
Name: Wahidur Rahman Rafsan (1518006) & Biswarup Goswami (1518017)
Group No.: 06
Date of Submission: 14.01.2019

Signature of Faculty:

10
Objective
The objective of this experiment was to-

Carry out in silico simulation by creating a Glucose-Insulin regulation model

subsystem
Understand how glucose and insulin concentrations in plasma are regulated
and they maintain homeostasis
Understand how to model Type-1 and Type-2 diabetes conditions in Simulink
software
Understand the mechanism how Type-1, Type-2 diabetes affect our body and
whether insulin can maintain that diabetes or not
Learn the mathematical relation between Renal Loss Rate, Tissue Utilization
Rate of Glucose (both insulin dependent and independent), Insulin Production
Rate, Insulin Destruction Rate and Glucose Flow Rate

Homework 1
The Simulink model of glucose-insulin regulation is provided below-
The subsystem block in the above given model contains another complex model which
is provided below-

Figure 1: Basic Model for simulating Glucose-Insulin regulation in human body

Figure 2: Glucose and Insulin Regulation Model

We simulated this model assuming three conditions

Firstly, Normal condition where there is no diabetes

Secondly, Type 1 diabetic condition

Thirdly, Type 2 diabetic condition

We will compare mainly two things of those above-mentioned condition-

1. Blood Glucose Concentration and

2. Blood Insulin Concentration

To compare, we will provide an initial intake of glucose in the human body

1. Glucose Infusion Rate

Figure 3:Graph of glucose infusion rate vs time for the three conditions.

Observation

We modeled the glucose infusion or intake by pulse generator. In all the three
conditions we mentioned, we have provided our subjects with same amount of
glucose. So, we have got a similar graph for all the conditions with a rectangular pulse
2. Blood Glucose Concentration

Figure 4:Response of blood glucose concentration to rapid infusion of glucose with time.

Observations and their explanations

We have found some notable observations from the plot above. Some of them are
mentioned below with necessary explanation below -

➢ The glucose concentration curve for both the type-1 and type-2 diabetes are
same and they overlap. In the type-1 diabetes, WBC of blood, destroys the
beta cell of pancreas. As a result, Insulin generation is stopped. So, insulin
can’t bind with receptor on cell and thus, glucose can’t go inside the cell. In
case of type-2, the insulin production may or may not be normal but glucose
uptake is not normal. In our experimental procedure, we have assumed that
there is no problem in insulin production but glucose uptake is abnormal.
 So, in both cases, glucose concentration remains constant although insulin
level changes. Hence the overlapping glucose concentration curves are
observed.
➢ The steady-state glucose level is higher in type-1 and type-2 diabetes than in
a normal patient. This happened because the initial condition value of
glucose in type-1 and type-2 diabetes was higher than in normal values.
Initial condition value of glucose, in normal condition = 0.81 mg/mL
in type 1 diabetic patient = 1.28 mg/mL
in type 2 diabetic patient = 1.29 mg/mL
➢ The decay of glucose concentration toward steady-state level after the
infusion is slower in type-1 and type-2 diabetic patient compared to a normal
patient because of the slower or no glucose going from plasma to cell.

➢ The glucose concentration curves for type 1 and type 2 diabetic patients do
not have the undershoot which is present in the curve for a normal person

3. Blood Insulin Concentration

Figure 5:Response of blood insulin concentration to rapid infusion of glucose with time.
Observations and their explanations

➢ Insulin concentration in type-2 diabetic patient is higher than it is in normal

patient which in turns is higher than the insulin concentration in type-1 diabetic
patient. As we have stated previously that, in type-1 insulin production is
inhibited but we assumed that there is no insulin production inhibition (only the
glucose uptake is abnormal). So, for type-1, the insulin level in plasma will surely
be less than type-2 and normal condition. This is clearly seen in the graph.
➢ Insulin concentration decay towards steady-state after glucose infusion is
slower in type 1 and type 2 diabetic patients than in normal patient.
➢ As we have used these data,
Initial condition value of insulin in normal condition = 0.05 mU/mL
in type 1 diabetic patient = 0.029 mU/mL
in type 2 diabetic patient = 0.146 mU/mL
So, the starting point of type-2 graph is higher than normal graph and
normal graph starts at higher level than type-1 condition
Homework 2

In this task, steady-state operating point was found out for normal condition, type-1 and type-2
diabetes conditions. Actually, we have to do two plots of Insulin concentration in plasma vs
Glucose concentration in plasma simultaneously on a single graph. One plot was when we are
taking the Insulin response to glucose infusion and another was for Glucose flow rate or
glucose mass balance equation.

The point where the two plots are intersected, is known as steady-state operating point for
glucose-insulin regulatory system. The steady-state operating points were different for three of
the different condition. We will see that; these operating points are very much closer to the
given initial conditions for each of the three cases. The two sets of equations and their
notations are given below-

𝑄𝐿 = 𝜆𝑥 + 𝜐𝑥𝑦 𝑤ℎ𝑒𝑛 𝑥 ≤ 𝜃

𝑄𝐿 = 𝜆𝑥 + 𝜐𝑥𝑦 + 𝜇(𝑥 − 𝜃) 𝑤ℎ𝑒𝑛 𝑥 > 𝜃

𝑄𝐿 − 𝜆𝑥 − 𝜇(𝑥 − 𝜃)
y=
𝜐𝑥
where 𝑄𝐿 = input flow rate

𝜆 = Glucose Consumption Co-efficient (insulin dependent)

𝜐 = Glucose Consumption Co-efficient (insulin independent)

𝑥 = Glucose Concentration (mg/mL)

𝑦 = Insulin Concentration (mU/mL)

𝜇 = Glucose Loss (via renal flow) Co-efficient

𝜃 = Threshold for Renal Loss of Glucose

And 𝑦 = 0 𝑤ℎ𝑒𝑛 𝑥 ≤ 𝜑

𝛽
𝑦 = 𝛼 (𝑥 − 𝜑) 𝑤ℎ𝑒𝑛 𝑥 > 𝜑

where 𝜑 = Threshold for Insulin Production

𝛽 = Insulin Production Co-efficient

𝛼 = Insulin Destruction Co-efficient

Matlab code :

close all;
clear all;
clc;

%Modeling the normal condition

theta=2.5; % this is the threshold for renal loss of glucose
beta=1430; % this is insulin production co-efficient. It will be decreased in type-1 but
remain same at type-2
alpha=7600; % this is insulin destruction gain
phi=0.51; % this is threshold for insulin production
Ql=8400; % this is input flow rate
nu=139000; % this is Glucose Consumption Co-efficient (insulin independent). this will
remain same at type-1 but will change in type-2
mu=7200; % this is Glucose loss (via renal flow) Co-efficient
lambda=2470; % this is Glucose Consumption Co-efficient (insulin dependent)

x=0:0.0001:2; % x is the glucose concentration in blood

y=(beta/alpha)*(x-phi); % y is the insulin concentration in blood as in the equation
y(find(x<phi))=0; %this is when y value is below threshold, phi

figure(1);
plot(x,y);
ylim([0 0.20]);
hold on;

y1=(Ql-lambda*x-mu*(x-theta))./(nu*x); % y1 is also the insulin concentration but when

are taking glucose mass balance consideration
y1(find(x<theta))=(Ql-lambda*x)./(nu*x);

plot(x,y1,'--');

%modeling for type1 diabetes

beta_t1=0.2*beta; % insulin production is inhibited so beta has reduced

y_type1=(beta_t1/alpha)*(x-phi); % y is the insulin concentration in blood

y_type1(find(x<phi))=0;

figure(2);
plot(x,y_type1);
ylim([0 0.20]);
hold on;
plot(x,y1,'--');

%Modeling type-2 diabetes

nu_t2=0.2*nu; % glucose consumption is reduced that means nu is reduced

figure(3);
plot(x,y);
ylim([0 0.20]);
hold on;

y1_t2=(Ql-lambda*x-mu*(x-theta))./(nu_t2*x); % y1 is also the insulin concentration

y1_t2(find(x<theta))=(Ql-lambda*x)./(nu_t2*x); % but expressed under different
considerations
plot(x,y1_t2,'--');

The corresponding graphs are attached in opposite page

1. Normal Condition

Fig 6: Steady-state Analysis of Glucose Regulation under Normal Condition

From the graph,

Steady-state level of glucose = 0.8114 mg/mL
Steady-state level of insulin = 0.05671 mU/mL
2. Type-1 Diabetes

Fig 7: Steady-state Analysis of Glucose Regulation under Type 1 Diabetic

Condition

From the graph,

Steady-state level of glucose = 1.283 mg/mL
Steady-state level of insulin = 0.02933 mU/mL
 3. Type-2 Diabetes

Fig 8: Steady-state Analysis of Glucose Regulation under Type 2 Diabetic

Condition

From the graph,

Steady-state level of glucose = 1.286 mg/mL
Steady-state level of insulin = 0.146 mU/mL

These steady-state values found graphically are almost equal to the initial conditions
provided in the Simulink simulation.