InsulinGlucagon Interactions: Using a Game To Understand

Hormonal Control
Colleen J. Conway* and Maureen Leonard
Department of Sciences, Mount Mary University, Milwaukee, Wisconsin 53233, United States
*S Supporting Information
ABSTRACT: Manipulative activities have been used by many
chemistry teachers to help students understand complex material
and are often presented as games. The game described here is an
in-classroom manipulative exercise that was devised to help
prehealth and predietetics undergraduate majors understand the
important concepts of the metabolic eects of the two
antagonistic hormones insulin and glucagon in regulating
human homeostasis. Student responses indicate that they believe
the game increases their understanding of these eects and that
they enjoyed playing the game. Pre and post activity assessments
showed a signicant dierence in understanding the eects of the
dierent hormones.
KEYWORDS: Second-Year Undergraduate, Hands-On Learning/Manipulatives, Analogies/Transfer, Hormones,
Humor/Puzzles/Games, Metabolism, Student-Centered Learning

INTRODUCTION
Insulin and glucagon are important hormones that help regulate
homeostasis, with multiple major eects on sugar and protein
metabolism in humans (Table 1).
1
These two hormones are
antagonistic, and so the reactions they control mirror each
other. Often, students have diculty understanding the eects
of the hormones if the information is presented as just all
lectures. A manipulative game was devised to illustrate the
dierent and opposite responses to these hormones within the
cell for a nonscience majors organic and biochemistry course.
Prehealth and predietetics students who take this course must
have a good understanding of these processes to succeed in
their careers but not to the same depth as a one- or two-
semester biochemistry course meant for biology, chemistry, and
biochemistry majors. Many college and universities are oering
these types of courses for prehealth and predietetics students in
preprofessional programs. The textbooks available for these
courses reect that level of information, with the processes
explained well but not at each step of every reaction in the
pathway.
1
This manipulative game provides a useful demon-
stration of the general principles of the antagonist interactions
of these hormones for such a course and could also be used as
an introduction to these concepts in majors courses as well. We
use the term game here to describe this activity as a fun and
dierent way to present the information; the game is not
competitive nor does it have multiple outcomes.

TEACHING METABOLIC HORMONE

INTERACTIONS THROUGH GAME PLAY
One advantage of using a game to demonstrate this information
is that it uses auditory, visual, and psychomotor learning styles,
thus increasing the learning and retention of information.
2
The
use of games also makes learning more fun and helps learners
take a more active role in their learning.
2
Games that are
interactive can help students collaborate to learn new material
and also review what they have learned in a dierent setting and
mode.
2
Games can also increase the amount of information that
is stored in the long term memory of students because of the
amount of thought and engagement that they are experiencing.
3
One advantage of games is the increase in both student-to-
student interactions and student-to-teacher interactions, such as
Published: March 18, 2014
Table 1. Metabolic Actions of Insulin and Glucagon
Typical
Order Insulin Acts To:
a
Glucagon Acts To:
a
1 Transport glucose into the cell
Start glycolysis Stop glycolysis
Stop gluconeogenesis Start gluconeogenesis
2 Start glycogen formation Stop glycogen formation
Stop glycogen breakdown Start glycogen breakdown
3 Start fatty acid and triglyceride
synthesis
Stop fatty acid and triglyceride
synthesis
Stop fatty acid and triglyceride
degradation
Start fatty acid and triglyceride
degradation
Stop ketone body formation Start ketone body formation
4 Start amino acid uptake No eect
Start protein synthesis No eect
Stop protein breakdown No eect
a
See ref 1.
Activity
pubs.acs.org/jchemeduc
2014 American Chemical Society and
Division of Chemical Education, Inc. 536 dx.doi.org/10.1021/ed300771t | J. Chem. Educ. 2014, 91, 536540
questions that show the amount of engagement of students in
learning and their interest in the material presented.
3
Games
are another method for students to learn important material.
4,5
Researchers have found that students using games performed
better when tested than did the traditional students who did
problem sets instead.
4
In the same research, all students
thought that games were an easier way to learn than problems.
4
The students that used the games said that seeing the material
improved their understanding.
4
Other chemistry teachers at both the college and high school
levels have used everyday, inexpensive objects in their games to
enhance student learning. In 1999, an article in this Journal
listed 64 dierent chemistry games.
6
A few newer examples use
paperclips to represent dierent atoms to make compounds,
7
LEGOs representing dierent ions to make ionic compounds,
8
beads to represent the ions of dierent types of acids,
9
small
balls to show redox reactions,
10
and candy to help in
determining kinetics.
11
The LEGO study assessed the students
who played the game in comparison to others and found that
the students who learned by playing games had higher scores
on a posttest than did students who learned the material from
lecture or an online game.
8
The researchers felt that the game
was an advantage because of the low cost of the items used, it
was fun, and the students performed better on assessments.
8
This game also uses inexpensive toys to denote dierent
chemical molecules and would not be expensive to set up and
use.
This game was designed to help visualize the complex
interactions of the hormones insulin and glucagon and their
regulative functions; we have used it after the students have
been exposed to the material from their textbook and in class
discussion.
1
The insulin and glucagon reactions are founda-
tional for these majors and must be clearly understood early in
the students education for success in their chosen careers, as
they play a critical role in normal metabolic function and in
many metabolic disorders, such as diabetes and hypoglycemia.
In general, insulin is released when blood sugar levels are
high, such as immediately after eating, to lower the blood sugar
levels by moving the sugars into the cell to be used to produce
ATP. This means that the metabolic process glycolysis will be
turned on. Gluconeogenesis, or production of sugar, will be
turned o. Glycogen formation is triggered as well, and
glycogen degradation is turned o. Fatty acids are made and
then turned into triglycerides, and fatty acid beta-oxidation is
stopped. Additionally, amino acids are taken up by cells and
made into proteins, as sucient energy and resources are
available for growth.
Glucagon has almost the opposite eects. It is released when
blood sugar levels are low to raise the blood sugar levels.
Glucagon turns on gluconeogenesis and stops glycolysis.
Glycogen degradation is turned on and glycogen synthesis
turned o. Fatty acids are degraded, and also some become
ketone bodies so that they can cross the bloodbrain barrier.
All these responses are to maintain cellular respiration and ATP
production. Glucagon has no eect on protein degradation
under normal eating conditions (Table 1).

IMPLEMENTING THIS ACTIVITY

Basic Game Components
The game begins on a large piece of paper or cardboard
representing a cell, generally about one meter by half a meter.
One side of the cell is intended for the insulin players and the
other for the glucagon players, with eight players in all for each
round of play. The cell membrane is demarcated as a wide
border, in which receptor proteins for insulin and glucagon are
represented with a physical model spanning the membrane.
This specic version uses toy boats anchored in the
membrane to demonstrate the integral receptor protein. This
metaphor can be modied easily by simply drawing receptors
on the membrane or using cardboard pieces, but these parts
should be designated as part of the membrane to properly
represent the protein. There are many such receptors in a given
membrane, which we represent here by having multiple boats
anchored. There is one receptor per metabolic pathway
described by the game.
When the hormone binds with the receptor protein, this
triggers an intracellular signaling pathway (described more
completely below in Game Play). In this formulation, when a
hormone (one of the people gures) binds to its receptor (one
of the larger boats), the receptor is activated and triggers the
intracellular signaling pathways (one of the small boats inside
the larger boat, Figure 1). This setup is not strictly necessary,
and other formulations can be employed, including moving
pieces representing one or more of the signaling molecules
depending on the depth of instruction. The layout for this
version of the game is pictured in Figure 1 (colors are
Figure 1. Picture of the game board for the insulinglucagon game. This shows all of the components of the game and their relative relation to one
another. The people on the left are insulin and on the right, glucagon. The large boats on the left are the insulin receptors and on the right are the
glucagon receptors. The boxes are the regulated reaction sites and hold the resulting molecules of that reaction. The cell membrane is the line
around the large white sheet of paper.
Journal of Chemical Education Activity
dx.doi.org/10.1021/ed300771t | J. Chem. Educ. 2014, 91, 536540 537
coincidental). This conguration emphasizes the relative
mobility of elements by using the boats as metaphors.
Inside the cell are four areas that represent the four types of
reactions the hormones regulate. This game uses physical boxes
called islands as these areas. These should be marked with the
reaction names, one on each side to represent the inverse
relationship between the two hormones. The reactions include:
glycolysis/gluconeogenesis; glycogen synthesis/glycogen
degradation; fatty acid-triglyceride synthesis/fatty acid-
triglyceride degradation; and protein synthesis/protein
degradation. The small boats that represent the signaling
cascade contain stop, go, and no eect tokens (Figure 2).
These tokens t over outlines drawn on each set of reactions
pairs (e.g., glycolysis/gluconeogenesis) in this formulation
(Table 2).
Inside the container are the molecules that result from
activating the metabolic pathway, which should be some
physical representation (Table 2). These can be physical
models, such as those pictured herein, or just paper with the
molecules names written on them (Figure 3). This version of
the game provides students with the resulting molecules that
are produced only after requiring them to make a decision on
which pathway is activated. Other variations are possible as well
and might require students to understand which molecules will
result from which reactions, depending on the depth of
instruction. See the Supporting Information for examples and
more details.
Game Play
The game begins by students reading a scenario in which the
person whose cell is represented by the game board either has
just awakened in the morning (fasting) or has just eaten
(because it is later in the day). This scenario requires the
students to decide which team, Insulin or Glucagon, should be
active. This reinforces the understanding of how blood sugar is
aected by food. Members of each team can activate their
pathways by moving their hormone to the membrane receptor
protein. This means that they put the insulin or glucagon
person in the large boat (the receptor), which then causes a
cascade of reactions to occur in the cell as represented by the
small boat sailing to the correct island and turning one
metabolic pathway on and another o. Each of the large boats
represents one set of opposing metabolic pathways, as does
each island. This is done to allow more student participation
and to help students think about each set of opposing pathways
separately.
Once the students have decided which team is playing,
members of that team will activate their pathway via the
membrane receptor and one of the small boats will travel to
each of the four islands. The order is generally irrelevant, but
Figure 2. Picture of the reaction site of glycolysis and gluconeogenesis.
Here gluconeogenesis is turned on with the green go token
showing and glycolysis is turned o with the red stop token. The
small boat is the intracellular signaling transduction of the hormone.
There is one glucose molecule that was released from the
gluconeogenesis reaction center, shown as the yellow star.
Table 2. Relationships in the Game among the Four Reaction Areas, Hormones, and Reaction Products
Reaction Area
Insulin Status
(Typical Order)
a
Glucagon Status (Typical Order)
a
Color/Shape of the Reaction Product
Representational Objects
b
Glycolysis Activated; Pyruvate
(2)
Repressed Yellow hearts
Gluconeogenesis Repressed Activated; glucose (1) Yellow star
Glycogen synthesis Activated; glycogen
chain (1)
Repressed Linked yellow stars
Glycogen degradation Repressed Activated; glucose (23) Yellow stars
Fatty acid and triglyceride
synthesis
Activated;
triglycerides (2)
Repressed Purple and pink owers linked with a clear
star
Fatty acid and triglyceride
degradation
Repressed Activated; fatty acids (3); glycerol (1); ketone bodies (23) Purple and pink owers; clear star; keys
Protein synthesis Activated; protein
chain (1)
No eect Linked purple, red, clear hearts
Protein degradation Repressed No eect
a
See Table 1 and ref 1.
b
See the Supporting Information for examples and more details.
Figure 3. Picture of the key to the molecules identity. These are the
tokens used in the game, and this key helps students to determine
what molecules are in each of the reaction centers when that reaction
center is activated and the molecules are removed. See the Supporting
Information for examples and more details.
Journal of Chemical Education Activity
dx.doi.org/10.1021/ed300771t | J. Chem. Educ. 2014, 91, 536540 538
the following is typically how the material is presented in texts
and will reinforce learning more readily:
1. Glycolysis/gluconeogenesis
2. Glycogen synthesis/glycogen degradation
3. Fatty acid-triglyceride synthesis/fatty acid-triglyceride
degradation
4. Protein synthesis/protein degradation
As the team visits each island, the students will decide
whether their hormone inhibits or activates each reaction and
why. Based on their choice, students will place the appropriate
stop, go, or no eect token on the reaction box. If a go
token is used, the students will remove the molecules from the
areas container and put them onto the game board inside the
cell. Once all four islands have been visited and the tokens have
been deployed, the groups will ask for their cells to be reviewed
by the instructor to ensure they have chosen correctly, both in
terms of which hormone team should have played and whether
that team chose the correct tokens for each reaction.
The instructor will facilitate an explanation of the students
decisions and a review of the actual metabolic processes
involved at this time as well. Specically, the metabolic
products of each reaction should be discussed by examining
which products were removed from the reaction box. A table of
this information is provided in the Supporting Information.
After this review, the instructor will provide the alternate
scenario and the game will be replayed. Usually the entire game
with both scenarios is played two to three times to ensure
clarity, with students swapping roles of insulin or glucagon. See
the Supporting Information for examples and more details.
Postgame Reection
Once the game has been played by both hormone teams, the
groups review their decisions again, using a worksheet as a
guide. The worksheet reviews the eects of these hormones on
the cell and on the individual in terms of human homeostasis.
The game allows students to visualize and manipulate objects
corresponding to the ideas presented in the text, providing a
kinesthetic approach to this material. The instructor can also
verbally reinforce the decision making throughout the game to
aid students. This multimodal exercise has been successful in
increasing student understanding and condence and clarifying
the actions of these hormones. Students often comment on
how the game helps them to visualize the big picture of the
hormone eects.

FEEDBACK FROM STUDENTS

Students who have used this game report an improved
understanding of these processes when asked to assess their
understanding before and after playing using a Likert scale of
17, in which 1 denotes strongly disagree with the presented
statement and 7 denotes strongly agree. The questions asked
how well the students understood the eects of insulin and
glucagon on the dierent pathways before and after the game
was played. The questions and the resulting gure are listed in
the Supporting Information. Student comments included these:
I learned a lot today!; I loved this game!; and The game
really helped [me] understand what insulin and glucagon do.
No negative comments were received.

ASSESSMENTS OF LEARNING
In an evaluation of student self-assessment of their learning and
in a pre- and postgame test, the students scored statistically
signicantly better after playing the game than before playing
the game. This dierence also occurred when students did
guided-inquiry activities on the same material, but the two
activities did not dier in their eectiveness. The questions
asked in the pre- and postgame assessment and the gure of the
results and statistical analyses are in the Supporting
Information.
Even when no dierences are seen between this and other
types of activities, there still may be utility in using games.
When pharmacy students played a game called Race to
Glucose, the researchers found no signicant dierence
between student performance on exam questions directly
related to the game and on questions that related to
information learned in lecture.
12
The authors of Race to
Glucose still felt that the students had learned using the game,
as peer learning could occur, even though there was no
signicant dierence between learning in class and with the
game.
12
The researchers also received quite positive comments
about the game from their students.
12
Having students excited
about learning was thought to be an adequate reason to play
games as it increased their enthusiasm for learning metabolic
pathways.
12
Students also interacted with each other and
helped each other learn and think through the material.
12
This
is similar to this game in that students are in charge of what
they are doing by moving the pieces and help each other to
grasp the eects of the two hormones. See the Supporting
Information for examples and more details.

CONCLUSIONS
This game has helped predietetic and prehealth students
visualize and understand the eects of insulin and glucagon on
metabolism. Not all students learn in the same way, and this is
another tool to increase understanding of these complex
mechanisms that occur in metabolism. This game could easily
be used as an introduction to these concepts in courses for
chemistry majors as well, with expected additional material as
needed in those courses.

ASSOCIATED CONTENT
*S Supporting Information
Step-by-step play in pictures and detailed explanations;
questions used in the pre- and postgame assessments with
the gure of that information; results of a one-way ANOVA for
the pre- and posttest and the questions. This material is
available via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION
Corresponding Author
*E-mail: conwayc@mtmary.edu.
Notes
The authors declare no competing nancial interest.

ACKNOWLEDGMENTS
Thanks to Mount Mary University, all the students in
Chemistry 206 classes, Patricia Ahrens, and Angela Sauro.

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