How does muscle store glucose?

From the Guidelines

Muscles store glucose primarily as glycogen, a complex carbohydrate made up of multiple glucose molecules linked together. This process is facilitated by insulin, which signals muscle cells to take up glucose from the blood, and then through glycogenesis, glucose molecules are joined together to form glycogen, serving as a readily available energy reserve 1.

Key Points About Muscle Glucose Storage

• When you consume carbohydrates, your body breaks them down into glucose, which enters the bloodstream.
• Insulin then signals muscle cells to take up this glucose from the blood.
• Inside the muscle cells, glucose molecules are joined together through a process called glycogenesis to form glycogen.
• This stored glycogen can be quickly broken down through glycogenolysis when energy is needed during physical activity, especially during high-intensity exercise.
• As noted in a joint position statement by the American College of Sports Medicine and the American Diabetes Association, muscular contractions stimulate glucose transport via a separate, additive mechanism not impaired by insulin resistance or type 2 diabetes 1.

Importance of Glycogen Storage

• Muscle glycogen storage is particularly important for athletes and physically active individuals, as it directly affects exercise performance and endurance.
• Regular physical activity increases muscle cells' ability to store glycogen, which is why trained athletes can often store more glycogen than untrained individuals.
• Consuming carbohydrates after exercise helps replenish these glycogen stores more efficiently, preparing muscles for future activity.

Clinical Implications

• Understanding how muscles store glucose is crucial for managing conditions like type 2 diabetes, where insulin-stimulated glucose uptake into skeletal muscle is impaired 1.
• A combination of aerobic and resistance exercise training may be more effective in improving blood glucose control than either alone, highlighting the importance of physical activity in glucose metabolism 1.

From the Research

Muscle Glucose Storage

• Muscle stores glucose in the form of glycogen, a branched polymer of glucose 2, 3, 4.
• The majority of glycogen is stored in skeletal muscles (∼500 g) and the liver (∼100 g) 3.
• Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through transporters, phosphorylation of glucose to glucose 6-phosphate, isomerization to glucose 1-phosphate, and formation of uridine 5'-diphosphate-glucose, which is the direct glucose donor for glycogen synthesis 4.
• Glycogenin catalyzes the formation of a short glucose polymer that is extended by the action of glycogen synthase, and glycogen branching enzyme introduces branch points in the glycogen particle at even intervals 4.

Glycogen Metabolism

• Glycogen is accumulated in the liver primarily during the postprandial period and in the skeletal muscle predominantly after exercise 4.
• Glycogen breakdown or glycogenolysis is carried out by two enzymes, glycogen phosphorylase which releases glucose 1-phosphate from the linear chains of glycogen, and glycogen debranching enzyme which untangles the branch points 4.
• The glucose 6-phosphatase system catalyzes the dephosphorylation of glucose 6-phosphate to glucose, a necessary step for free glucose to leave the cell 4.
• Mutations in the genes encoding the enzymes involved in glycogen metabolism cause glycogen storage diseases 4.

Regulation of Glycogen Metabolism

• Glycogen regulation takes place not only by allosteric regulation of enzymes, but also due to other factors such as subcellular location, granule size, and association with various glycogen-related proteins 5.
• Two metabolically distinct forms of glycogen, pro- and marcoglycogen have been identified that vary in their carbohydrate complement per molecule and have different sensitivities to glycogen synthesis and degradation 5.
• Exercise-induced muscle glucose uptake is regulated by the translocation of GLUT4 glucose transporter to the plasma membrane and T-tubules upon muscle contraction 6.
• Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part 6.