Republic of Gamers

Homeostasis
Internal
BIO 3.4
(91604)
Blood Glucose Regulation
Part One

Strategies for
Success
MAKE SURE YOU READ
THE PRESENTER NOTES
BELOW EACH SLIDE.
USE THE FEEDBACK
LOOP MODEL.
USE THE ESSAY STRUCTURE
TEMPLATE TO HELP
ORGANIZE YOUR NOTES
AND REPORT.
SEND ME QUESTIONS VIA
CHAT AND SUBMIT YOUR
DRAFT WORK VIA
ASSIGNMENT.
COLLABORATE AND
ASK FOR HELP.
DON’T PLAGIARISE!
= details for
Achieve
Must
Read
Should
Do
= details for Merit and
Excellence

Know the components of the
feedback loop and how they
work together as a system.
This is where the
scenario comes in
Must
Read

Image from Wikicommons
The most crucial energy source between meals is glucose. Many critical organs such as the
brain and the nervous system are totally reliant on having a certain level of glucose to function
properly so of all the nutrients available to the body the levels of glucose are the most tightly
regulated by homeostatic mechanisms and glucose is the only carbohydrate we store in any
significant amount.
Oxygen
Food provides the energy we need to live
All of our ATP comes from the food we eat
and the vast majority of this will be in the
form of carbohydrates, fats or proteins.
Most carbohydrate in our diet is either
starch (which is long chains of glucose),
lactose (disaccharide in milk composed of
glucose linked to galactose) and sucrose
(dimer of glucose and fructose) or just plain
fructose or glucose.
Must
Read

Metabolism of Glucose is Via Glycolysis and the Krebs
Cycle
KREBS CYCLE (Lots of ATP via respiration)
ATP ATP ATP ATP ATP ATP ATP ATP
ATP
ATP
Basic glycolysis
scheme above from
Sciencemusicvideos
Must
Read

The Scenario and Report Template
(1) Select two parts of Tania’s day to link the scenario to two different manageable disruptions.
The scenario helps provide a context to how the homeostatic system works in response to
changes in the external and internal environments.
(2) Using a hypothetical situation involving Tania is perfectly acceptable, especially when you are
relating to a breakdown of the homeostatic system.
(3) Use the homeostasis essay structure template (in TEAMS) to help you research and plan
your essay. Make sure your report is concise and easy-to-follow.
(4) Read the Thermoregulation exemplar (low excellence) and teacher comments to get a feel
for the level of detail required at Level 3.
Must
Read

Basic Report Structure – FOLLOW THE GLUCOSE MOLECULES!!!
Must
Read
Introduction Level
What are the normal levels of blood glucose throughout the day. Achievement
Reasons for homeostasis and blood glucose regulation. Achievement
Manageable Disruption 1 - Increase in blood glucose negative feedback system
Scenario 1 linked to feedback loop. Achievement
Overview of what each component is in this system. Achievement
Details of what happens at each component (what triggers what) and significance. Merit
Managable Disruption 2 - Decrease in blood glucose negative feedback system
Scenario 2 linked to feedback loop. Achievement
Overview of what each component is in this system overview of system Achievement
Details of what happens at each component (what triggers what) ) and significance. Merit
Breakdown – Diabetes
Scenario 3 linked to breakdown of feedback loop.
Merit
Overview of what causes diabetes and symptoms.
Details of what happens during breakdown and significance. Excellence

Key biological
ideas to discuss
at
Merit/Excellence
:
 Facilitated diffusion and GLUT transporters
 Concentration gradient
 Depolarisation in Beta cells
 Exocytosis
 Glycogenolysis, Glycogenesis, Gluconeogenesis
 Hormones and Signal transduction pathway
 Phosphorylation
 Hyperglycemia and Hypoglycemia
 Ketoacidosis
Should
Do

Key Terms You need to Know (and
define)
Homeostasis Alpha cells Glycolysis Set point
Negative feedback
loop
Beta cells Glycogen Hypoglycemic
Receptor Insulin Glucagon Hyperglycemic
Controller Hormone Glycogenolysis
Type 1 & Type 2
Diabetes
Effector GLUT Transporter Glycogenesis Ketoacidosis
Variable Facilitated diffusion Gluconeogenesis
Manageable
disruption
Exocytosis Phosphorylation
Breakdown Ion channels
Must
Read

Normal range of glucose concentration
Value range Unit
0.07 -0.10 percent (%)
70 – 100
milligrams per hundred cubic
centimetres (mg 100 cm-3) =
milligrams per decilitre (mg dL-1)
3.9 – 5.4
millimoles per litre
(mmol L-1 or mM)
Must
Read

Regulating blood glucose
levels
Why it’s important not to let blood glucose levels get too high or low
(adaptive advantage)

Glucose Homeostasis
Why is it important to not let it drop too low?
Some tissues can use a range of energy sources such as fats and
even amino acids but several important tissues in the body can only
really use glucose
These tissues include:
 red blood cells and immune cells
 Brain and the nervous system also
Therefore, maintaining a certain level of glucose is a
matter of life and death.
Must
Read

PET (Positron Emission Tomography)
imaging is a technique using
radioactively labeled glucose to
identify tissues in the body that use
lots of glucose
A Graphic Demonstration of How Much Glucose
the Brain Actually Uses
Brain
Tumors
Interesting Extra Information
Liver

Glucose Homeostasis
Why is it important to not let it get too
high?
 Do not want to waste glucose obtained by letting it leave the body
through urine
 So we need glucose all the time but we can’t eat all the time so we
need a system for storing glucose.
 The main place we store glucose is in the liver and we can store
enough there to keep us going for 2-3 days.
 Smaller amounts are taken into muscle and fat cells and either
used immediately or stored.
 This is all stimulated by insulin and is the way blood glucose
levels are kept low .
© Peter Shepherd 2012 – Permission granted for use for teaching purposes
Liver
Must
Read

But high blood glucose levels are dangerous as they
seriously damages some of our major organs over time
Kidneys Eye Blood vessels
Glucose can react with
and damage proteins in
blood stream and
vessels so tissues don’t
get the nutrients and
oxygen needed. Immune
systems weakens.
Must
Read

Why it’s important not to let blood glucose levels to get too high
or low (adaptive advantage)
If glucose levels get too low:
 Cells and organs, such as the brain, nerves, red blood cells,
immune cells which rely on glucose will stop functioning = go into
shock and eventually death
If glucose levels get too high:
 Don’t want to lose glucose through urine as cells are reliant to
have some glucose all the time
 If glucose levels stay too high for a long time, it can cause
damage to key organs - won’t cause death straight away but can
cause damage that can lead to lower quality of life and then
premature death.
Must
Read

Glucose is absorbed into cells though
facilitated diffusion
• Recall what is facilitated diffusion? Add an annotated
diagram here. Why can’t glucose simply diffuse through the
cell membrane?
Should
Do

Glucose
How Glucose Uptake Works in some tissues Including Brain and Liver
Outside
Cell
Inside
Cell
Glucose
transporters are
always present
in the plasma
membrane in
most cells
Glucose cannot cross the plasma membrane unless the membrane has specific proteins in
the membrane called glucose transporters (GLUT proteins)
These have pores allowing glucose to cross membranes by facilitated diffusion and flow
from areas of high glucose to areas of low glucose concentration until an equilibrium is
reached.
If glucose is continually being used as in the brain and nerve cells then there will always be
low glucose levels in the cell so it will keep flowing into the cell.
THIS IS FOR CELLS USING GLUCOSE NOT STORING IT
Should
Do

Glucose Transporters (GLUTs in the
Body)
Please note: There are many more kinds of glucose transporters but GLUT4 is the most important for BG regulation
Glucose is a hydrophilic molecule so cannot pass easily through the cell membrane without the
help of these protein channels (via facilitated diffusion).
Should
Do

The storing
and releasing
of glucose
 Involves a balance of two
hormones: Insulin and
Glucagon
•  cells involved in
insulin pathway
•  cells involved in
glucagon pathway
Must
Read

What are
hormones?
Insulin
Should
Do
Do you recall protein synthesis and exocytosis?

How do hormones work?
Should
Do

Must
Read
Complete the
feedback loop
flow chart

When blood
glucose levels
are high (after
a meal)
Feedback loop - increase in
variable (blood glucose)

The liver is
where our
body sorts all
the food and
also where it
stores
glucose
Must
Read

Stomach
All our food goes firstly into
stomach….
Must
Read

Small
intestines
…..then the small intestine……
Polymers (e.g. starch) must
be broken down by enzymes
before they can diffuse
through intestinal cells into
the blood stream.
Must
Read

LIVER
……then absorbed into special blood
vessels that take it directly to the liver
before it gets anywhere else
Must
Read

Insulin is made in only one place
in the body
Pancreas
5% of the cells in pancreas are
called beta-cells and the main
job of these is to make insulin
Less that 1 gram of beta cells in
your whole body.
Stomach
Liver
Must
Read

LIVER
…. Which stimulates the release of
insulin along the way Must
Read

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Th
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Cys
Cys
Gln
Glu
Val
Ile
Gly
Th
r
Lys
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Th
r
Ty
r
Ph
e
Ph
e
Gly
Ar
g
Glu Gly
Cys
Val
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Ty
r
Leu Ala
Glu
Val
Leu
His
Se
r
Cys
Gly
Leu
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Gln
As
n
Val
Ph
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S
S
S
S
S
S
High
Glucose
Stores
glucose and
so lowers
blood glucose
levels
Insulin is protein released by β-cells when blood
glucose levels rise and it lowers blood glucose
levels by stimulating uptake into 3 tissues
Must
Read

By being able to take up and store glucose
when insulin is high and later release it when
insulin is low the liver is the major organ
responsible for regulating blood glucose levels
32
Must
Read

What happens to glucose when it gets to
the liver if there is no insulin present ?
Glucose from
the gut
Glucose
Without insulin all the glucose goes
through the liver to the rest of the
body and is not stored
Must
Read

Glucose
Most important thing insulin does is to stimulate storage
of glucose in the liver after a meal. This lowers blood
glucose and provides a store of glucose for period
between meals
Some of the
glucose stored
as glycogen
Insulin
Glucose
Some of the glucose goes through
into main bloodstream
Must
Read

Glucose
Glucose is released into the blood
stream so organs like the brain can
keep functioning
Glucose stored
as glycogen
The glucose stored in the liver is released between
meals to keep blood glucose levels stable Must
Read

Two other important targets of
insulin are muscle and fat tissues
Must
Read

Without insulin not much glucose
gets into muscle and fat tissues
Glucose
Glucose
Must
Read

When insulin is present lots of glucose gets into
muscle and fat tissues and this helps lower blood
glucose after a meal
Insulin
Glucose
Insulin
Glucose
Must
Read

What Happens After a Meal
 Glucose levels in the portal vein (i.e the vein that comes directly from gut
to the liver) rise rapidly so glucose levels in the pancreas rise and insulin is
released from β-cells.
 Insulin binds to receptors that are found on cells in the liver, in muscle and
in fat cells
 This stimulates the uptake of glucose into these tissues so blood glucose
levels go down
 Glucose taken up by liver is mostly stored as glycogen
 Some of the glucose going into fat cells is turned into glycerol and so
contribute to the accumulation of fat in these cells.
 Some of the glucose going into muscle is stored as glycogen but tends to be
used very rapidly afterwards
Must
Read

Blood Glucose Feedback
VARIABLE – Blood Sugar Levels Increase
RECEPTOR – Receptors (Beta Cells in the Islets of Langerhans)
in Pancreas identify increase of blood sugar
CONTROLLER – Beta Cells in the Pancreas secrete the hormone
Insulin
EFFECTOR – Insulin receptors in the liver, muscle or fat cells
uptakes and converts Glucose and stores it
RESPONSE – Blood sugar levels decrease
FEEDBACK
–
Return
to
homeostasis
when
blood
sugar
levels
fall
returns
to
steady
state
Must
Read

Blood Glucose and Insulin
 The next set of slides are graphs that shows changes in blood glucose and
insulin levels after a meal. Keep track of the time things take to change. A
good way to link in the scenario.
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Time after a meal (in minutes)
After a meal blood glucose levels rise as glucose is
taken up by the gut but rapidly falls back to a set
point (i.e a homeostatic mechanism is in action).
How is this achieved and why is it important ?
Blood
Glucose
Concentration
(mM)
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Blood
Glucose
Concentration
(mM)
To be able to compare blood glucose
levels we usually assess this after an
overnight fast as after this amount of
time every ones glucose has come to
their homeostatic set point which we
call their “Fasting blood glucose levels”.
This is about 5 mM in humans
Blood Glucose Changes After a Meal
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Blood
Glucose
Concentration
(mM)
Insulin secretion starts
Blood glucose levels start
to rise after a meal
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Blood
Glucose
Concentration
(mM)
Insulin starts to work
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Feedback mechanisms
act to lower blood glucose
Blood
Glucose
Concentration
(mM)
Peak blood glucose
level after a meal
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Fasting blood glucose level
Blood
Glucose
Concentration
(mM)
Insulin feedback mechanisms
Peak blood glucose
level after a meal
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Peak blood glucose
level after a meal
Feedback mechanisms
is reached again
Blood
Glucose
Concentration
(mM)
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
Peak blood glucose
level after a meal
Feedback mechanisms
Blood
Glucose
Concentration
(mM)
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
With all this insulin coming into the
system how come the insulin doesn’t
just make the blood glucose levels
fall below 5mM
Blood
Glucose
Concentration
(mM)
?
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
1. As blood glucose levels fall less
insulin is secreted so insulin receptors
on cells shut off quickly. This is an
example of feedback regulation
Blood
Glucose
Concentration
(mM)
2. If blood glucose levels do fall below 5 mM
then a second hormone called glucagon is
secreted which causes glucose to be released
from stores held in the liver and so this raises
blood glucose levels again
Must
Read

1
5
3
4
2
6
7
8
9
30 60 90 120 150 180
1. As blood glucose levels fall less
insulin is secreted. This is an example
of feedback regulation
Blood
Glucose
Concentration
(mM)
2. If blood glucose levels do fall below 5 mM
then a second hormone called glucagon is
secreted which causes glucose to be released
from stores held in the liver and so this raises
blood glucose levels again
Why Do Glucose Levels Stabilise
Must
Read

Watch these videos to help understand
the basics of blood glucose regulation:
• https://www.youtube.com/watch?v=X78C5ajmKJs&ab_chann
el=TamerShabaan

Zooming in…
… on insulin pathway

Zooming in to role of Pancreas
Watch this video to find out the role the
pancreas plays in our bodies:
What does the pancreas do?

The Islets of Langerhans are the Central
Regulator of Insulin and Glucagon Levels
Islet cell structure
Insulin and glucagon are both hormones made only in a
special group of cells in the pancreas called the Islets
of Langerhans (or islets for short).
• The islets contain several cell types but the most
important are the α-cells - the only cells in the body
to make glucagon. These cells sense when blood
glucose falls below 5 mM and release glucagon.
• β-cells are the only cells in the body that make
insulin. They sense when blood glucose rises above 5
mM and release insulin.
The pancreas is adjacent to the gut and on the portal
vein which drains nutrients from gut to liver.
This means islets are very well placed to sense an
influx of nutrients and to respond by releasing
hormones.
Must
Read

Glucose
We need to release insulin very
quickly (within a few minutes)
but it takes 30-60 minutes for
the insulin gene to be switched
on and for new insulin protein to
be made. This is too slow so the
-cells make insulin in advance
and package it in vesicles just
waiting for the increase in
glucose levels to occur.
β-cells Store Insulin in Prepackaged Granules Ready For
Instant Release When Blood Glucose levels Rise
Outside
Cell
Inside
Cell
Should
Do

Glucose
The extra glucose coming
into the -cell triggers the
insulin containing vesicle to
move the the plasma
membrane and to fuse with
the plasma membrane , so
releasing the contents (i.e
the insulin) to the
bloodstream
How is Insulin Released from β-cells
Outside
Cell
Inside
Cell
Should
Do

Outside
Cell
Inside
Cell
How is Insulin Released from β-cells
The extra glucose coming into
the -cell triggers the insulin
containing vesicle to move the
the plasma membrane and to
fuse with the plasma
membrane , so releasing the
contents (i.e the insulin) to the
bloodstream
Should
Do

How do Beta cells detect glucose levels? Should
Do

FYI: this is how vesicles translocate (move) to the cell
membrane. Aren’t they just the coolest little robots
you have ever seen. YouTube ‘motor proteins’
and watch an animation of them in action. Obviously
not necessary for this internal.
For interest sake only!

Signal Transduction - Insulin binding with the
receptor
 Insulin moves through the blood stream until it finds its
specific receptor on the surface of the liver cells, muscle
cells and fat cells.
 The binding of insulin causes change in the shape of the
intracellular portion of the receptor which activates an
enzymatic activity.
 The receptor is now said to be activated and this brings
about changes inside the cell.
Should
Do

How insulin works on target cells
(effector)
Should
Do

Insulin
Receptor
Insulin
How Does insulin Stimulate Glycogen Synthesis in Liver
O
O
H
CH2OH
O
H O
H
O
H
O
O
H
CH2OH
O
H O
H
O
H
O
O
H
CH2OH
O
H O
O
H
O
O
H
CH2OH
O
H O
H
O
H
Glycogen
Synthase
Glucose
Outside
Cell
Inside
Cell
O
O
H
CH2OH
O
H O
H
O
H
O
O
H
CH2OH
O
H O
H
O
H
Should
Do

Insulin
Receptor
How Does insulin Stimulate Glycogen Synthesis in Liver
Glycogen
Synthase
Outside
Cell
Inside
Cell
O
O
H
CH2OH
O
H O
H
O
H O
O
H
CH2OH
O
H
O
H
O
O
H
CH2OH
O
H
O
O
H
CH2OH
O
H
O
H
O O O
Glycogen
O
O
H
CH2OH
O
H O
H
O
H
O
O
H
CH2OH
O
H O
H
O
H
Should
Do

Insulin
Receptor
Glucose
Vesicles
containing
GLUT4 glucose
transporter
Insulin
How Does insulin Stimulate Glucose Uptake Into Muscle And Fat Cells
Outside
Cell
Inside
Cell
Should
Do

Glucose
How Does insulin Stimulate Glucose Uptake Into Muscle And Fat Cells
Outside
Cell
Inside
Cell
Should
Do

Insulin
Receptor
Insulin
How Does Insulin Work and How is the Signal Shut Off
Outside
Cell
Inside
Cell
Receptor’s
Enzyme
Activated
Should
Do

Outside
Cell
Inside
Cell
Insulin receptor starts
to internalise into a
vesicle pinched off from
the membrane
Should
Do

Outside
Cell
Inside
Cell
H+
H+
H+
H+
H+
H+
H+
• The vesicle containing the insulin receptor
acidifies
• This changes the protein structure (see year
12 Cells chapter)
• Insulin can no longer bind to its receptor
• Insulin signal shut off
Should
Do

When blood glucose
levels are low
(between meals)

Antagonistic Hormones
 The effects of one hormone are often counteracted by an
opposing hormone, this is known as antagonistic hormones.
 Feedback mechanisms adjust the balance of the two hormones to
maintain physiological function.
Example: insulin decreases blood glucose and glucagon raises it.
Insulin
secretion
Glucagon
secretion
Raises blood
glucose level
Lowers
blood
glucose level
Decrease in blood
glucose stimulates
glucagon release
Increase in blood
glucose stimulates
insulin release
Must
Read

Antagonistic Hormones
Insulin Glucagon
 Produced by β-cells of
the Pancreas
 Produced by α-cells of
the Pancreas
 Released into
circulatory system when
blood glucose is high
 Released into the
circulatory system when
blood glucose is low
 Facilitates the
transport of glucose
into target cells
 Signals the liver to
break down glycogen
into simple glucose
Must
Read

Blood Glucose Feedback
INPUT – Blood Sugar Levels Decrease
RECEPTOR – Receptors (Alpha Cells in the Islets of
Langerhans) in Pancreas identify decrease of blood sugar
CONTROLLER – Alpha Cells in the Pancreas secrete the
hormone Glucagon
EFFECTOR – The Liver breaks down Glycogen converts the
Glycogen into Glucose and releases it back into the
bloodstream
RESPONSE – Blood sugar levels increase
FEEDBACK
–
Return
to
homeostasis
when
blood
sugar
levels
rise
returns
to
steady
state
Must
Read

How does glucagon stimulate glycogen breakdown
and release of glucose from the liver
 Glucagon binds to its receptor on the surface of liver cells and
activates signaling pathways that result in the activation of an
enzyme called glycogen phosphorylase which catalyses the
breakdown of glycogen polymers back into glucose.
 Glucose levels build up in the liver cells and when they exceed the
concentration outside the cells then the glucose moves out into
the bloodstream by facilitated diffusion through the glucose
transporters.
 Since glucagon is stimulating the breakdown of lots of glycogen
this means there is a constant flow of glucose out of the liver as
long as glucagon is around.
Should
Do

Glucagon
Receptor
Glucagon
How Does Glucagon Stimulate Glycogen Breakdown
in Liver and Release Glucose Into the Blood
O
O
H
CH2OH
O
H O
H
O
H O
O
H
CH2OH
O
H
O
H
O
O
H
CH2OH
O
H
O
O
H
CH2OH
O
H
O
H
O O O
Glycogen
Glycogen
Phosphorylase
Outside
Cell
Inside
Cell
Should
Do

Glucagon
Receptor
Glucagon
How Does Glucagon Stimulate Glycogen Breakdown
in Liver and Release Glucose Into the Blood
O
O
H
CH2OH
O
H O
H
O
H O
O
H
CH2OH
O
H
O
H
O
O
H
CH2OH
O
H
O
O
H
CH2OH
O
H
O
H
O O O
Glycogen
Glycogen
Phosphorylase
O
O
H
CH2OH
O
H O
H
O
H
O
O
H
CH2OH
O
H O
H
O
H
O
O
H
CH2OH
O
H O
O
H
O
O
H
CH2OH
O
H O
H
O
H
Glucose
Outside
Cell
Inside
Cell
O
O
H
CH2OH
O
H O
H
O
H
Should
Do

100grams
of glucose
Muscle 25g
Brain 17g
Kidney 9g
Used
immediately
Muscle 26g
Adipocytes 2g
Liver 21g
Stored
for later
Where does the glucose go ?
(exact figures depend on a person muscle and fat mass but a typical example is shown below)
Must
Read

FOLLOW THE GLUCOSE
MOLECULES!!

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