NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE “I Hate Running!” by Rhodes, Rozell, & Wilson
Part I — Blood, Skeletal Muscle Cells, and Glucose Uptake
To untangle the misconceptions in the conversation between Shelby and Patrick, let’s begin by looking at the structures
within skeletal muscle cells that are involved in energy production at a submaximal level of exercise in an untrained
person. This would be the case for Shelby, who is just beginning an aerobic exercise program that includes mostly
endurance training occurring in 20–30 minute bouts. In addition, let’s examine some common metrics such as lactate
threshold and blood pH to assess what is happening in an untrained person during exercise.
During the first 30 minutes of Shelby and Patrick’s run at a submaximal level (40–70% VO2 max), blood glucose levels
increase due to glucose release from the liver (Zinker et al., 1990), providing skeletal muscle cells with a concentration
gradient of glucose for uptake and subsequent ATP production. However, glucose is a large polar molecule and cannot
simply diffuse unaided into the sarcoplasm through the phospholipid bilayer comprising the sarcolemma of skeletal
muscle cells. Instead, to take up blood glucose, skeletal muscle cells must produce and insert glucose transporters,
commonly referred to as GLUTs, into their sarcolemma. These GLUTs are a diverse family of large, integral membrane
proteins that permit facilitated diffusion of glucose down its concentration gradient. Skeletal muscle cells can express
several different forms of GLUTs, but the most common form is GLUT4 (Gaster et al., 2000; Goodwin, 2010;
Richter & Hargreaves, 2013). Interestingly, the insertion of GLUT4 into the sarcolemma can either be stimulated by
insulin binding to its receptor on skeletal muscle cells that are resting, or by an insulin-independent mechanism during
contraction of the skeletal muscle cells (Richter & Hargreaves, 2013).
Activity 2
Using the information above, complete the flow chart (Figure 1) on the following page to get a better understanding
of the sequence of events that occurs during exercise. Then label all structures shown in the diagram (Figure 2), which
represents a portion of a skeletal muscle cell’s sarcolemma during exercise. Also label the extracellular fluid compart–
ment, blood, and sarcoplasm. Indicate where in the body glucose and insulin would have come from and how they are
transported to the skeletal muscle cell.
Questions
1. Why does glucose uptake by a skeletal muscle cell require a transporter such as GLUT4? In other words, why isn’t
simple diffusion possible?
2. What stimulates the insertion of GLUT4s into the sarcolemma?
3. The existence of GLUT4s in the sarcolemma does not guarantee glucose uptake into the cell. Why? What else is
required?
4. Exercise helps reduce blood glucose levels in people, even if they are insulin resistant and thus their cells can no
longer respond to insulin efficiently. How is this possible?
