Why does glucose uptake by a skeletal muscle cell require a transporter such as GLUT4? In other words, why isn’t simple diffusion possible?

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 , blood glucose levels increase due to glucose release from the liver , 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 . 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 .

Questions

⦁ Why does glucose uptake by a skeletal muscle cell require a transporter such as GLUT4? In other words, why isn’t simple diffusion possible?

⦁ What stimulates the insertion of GLUT4s into the sarcolemma?

⦁ The existence of GLUT4s in the sarcolemma does not guarantee glucose uptake into the cell. Why? What else is required?

⦁ 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?