Insulin–Glucagon Interactions: Using a Game To Understand

Activity pubs.acs.org/jchemeduc

Insulin−Glucagon 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 effects 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 effects and that they enjoyed playing the game. Pre and post activity assessments showed a significant difference in understanding the effects of the different hormones. KEYWORDS: Second-Year Undergraduate, Hands-On Learning/Manipulatives, Analogies/Transfer, Hormones, Humor/Puzzles/Games, Metabolism, Student-Centered Learning

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INTRODUCTION Insulin and glucagon are important hormones that help regulate homeostasis, with multiple major effects on sugar and protein metabolism in humans (Table 1).1 These two hormones are

their careers but not to the same depth as a one- or twosemester biochemistry course meant for biology, chemistry, and biochemistry majors. Many college and universities are offering these types of courses for prehealth and predietetics students in preprofessional programs. The textbooks available for these courses reflect 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 demonstration 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 different way to present the information; the game is not competitive nor does it have multiple outcomes.

Table 1. Metabolic Actions of Insulin and Glucagon Typical Order 1

2 3

4

a

Insulin Acts To:a

Glucagon Acts To:a

Transport glucose into the cell Start glycolysis Stop gluconeogenesis Start glycogen formation Stop glycogen breakdown Start fatty acid and triglyceride synthesis Stop fatty acid and triglyceride degradation Stop ketone body formation Start amino acid uptake Start protein synthesis Stop protein breakdown

Stop glycolysis Start gluconeogenesis Stop glycogen formation Start glycogen breakdown Stop fatty acid and triglyceride synthesis Start fatty acid and triglyceride degradation Start ketone body formation No effect No effect No effect

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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 different 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-tostudent interactions and student-to-teacher interactions, such as

See ref 1.

antagonistic, and so the reactions they control mirror each other. Often, students have difficulty understanding the effects of the hormones if the information is presented as just all lectures. A manipulative game was devised to illustrate the different 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 © 2014 American Chemical Society and Division of Chemical Education, Inc.

Published: March 18, 2014 536

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Figure 1. Picture of the game board for the insulin−glucagon 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.

stopped. Additionally, amino acids are taken up by cells and made into proteins, as sufficient energy and resources are available for growth. Glucagon has almost the opposite effects. 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 off. Fatty acids are degraded, and also some become ketone bodies so that they can cross the blood−brain barrier. All these responses are to maintain cellular respiration and ATP production. Glucagon has no effect on protein degradation under normal eating conditions (Table 1).

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 different chemistry games.6 A few newer examples use paperclips to represent different atoms to make compounds,7 LEGOs representing different ions to make ionic compounds,8 beads to represent the ions of different 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 different 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 foundational 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 off. Glycogen formation is triggered as well, and glycogen degradation is turned off. Fatty acids are made and then turned into triglycerides, and fatty acid beta-oxidation is

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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 specific version uses toy boats “anchored” in the membrane to demonstrate the integral receptor protein. This metaphor can be modified 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 figures) 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 537

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coincidental). This configuration 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 acidtriglyceride degradation;” and “protein synthesis/protein degradation”. The small boats that represent the signaling cascade contain “stop,” “go,” and “no effect” tokens (Figure 2). These tokens fit over outlines drawn on each set of reactions pairs (e.g., glycolysis/gluconeogenesis) in this formulation (Table 2).

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.

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 affected 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 off. 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 “off” 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.

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

Table 2. Relationships in the Game among the Four Reaction Areas, Hormones, and Reaction Products Reaction Area Glycolysis Gluconeogenesis Glycogen synthesis Glycogen degradation Fatty acid and triglyceride synthesis Fatty acid and triglyceride degradation Protein synthesis Protein degradation a

Insulin Status (Typical Order)a

Color/Shape of the Reaction Product Representational Objectsb

Glucagon Status (Typical Order)a

Activated; Pyruvate (2) Repressed Activated; glycogen chain (1) Repressed Activated; triglycerides (2) Repressed

Repressed

Yellow hearts

Activated; glucose (1) Repressed

Yellow star Linked yellow stars

Activated; glucose (2−3) Repressed Activated; fatty acids (3); glycerol (1); ketone bodies (2−3)

Yellow stars Purple and pink flowers linked with a clear star Purple and pink flowers; clear star; keys

Activated; protein chain (1) Repressed

No effect

Linked purple, red, clear hearts

No effect

See Table 1 and ref 1. bSee the Supporting Information for examples and more details. 538

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significantly better after playing the game than before playing the game. This difference also occurred when students did guided-inquiry activities on the same material, but the two activities did not differ in their effectiveness. The questions asked in the pre- and postgame assessment and the figure of the results and statistical analyses are in the Supporting Information. Even when no differences 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 significant difference 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 significant difference 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 effects of the two hormones. See the Supporting Information for examples and more details.

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 effect” token on the reaction box. If a “go” token is used, the students will remove the molecules from the area’s 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. Specifically, 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.

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CONCLUSIONS This game has helped predietetic and prehealth students visualize and understand the effects 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.

Postgame Reflection

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 effects 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 confidence and clarifying the actions of these hormones. Students often comment on how the game helps them to visualize the big picture of the hormone effects.

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ASSOCIATED CONTENT

S Supporting Information *

Step-by-step play in pictures and detailed explanations; questions used in the pre- and postgame assessments with the figure 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.

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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 1−7, in which 1 denotes “strongly disagree” with the presented statement and 7 denotes “strongly agree”. The questions asked how well the students understood the effects of insulin and glucagon on the different pathways before and after the game was played. The questions and the resulting figure 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.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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

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REFERENCES

(1) Denniston, K. J.; Topping, J. J.; Caret, R. L. General, Organic, and Biochemistry, 7th ed.; McGraw-Hill Companies: New York, 2011. (2) LeCroy, C. Games as Innovative Teaching Strategy for Overactive Bladder and BPH. Urol. Nurs. 2006, 26 (5), 381−385.

ASSESSMENTS OF LEARNING In an evaluation of student self-assessment of their learning and in a pre- and postgame test, the students scored statistically 539

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