Glycogen: the forgotten cerebral energy store

Area of Science:

• Neuroscience
• Metabolic Biochemistry
• Endocrinology

Background:

• Brain glycogen concentration is lower than muscle but higher than cerebral glucose.
• The precise role of brain glycogen remains largely unknown, though influenced by neural activity and hormones.
• Previous assumptions discounted brain glycogen as a significant energy store due to its low concentration.

Purpose of the Study:

• To review recent experimental evidence highlighting the importance of brain glycogen as a glucose reserve.
• To explore the potential role of brain glycogen in metabolic states and disease complications.

Main Methods:

• Review of experimental evidence concerning brain glycogen concentration, utilization, and regulation.
• Analysis of glial glycogen's role during hypoglycemia and its contribution to neuronal fuel supply.
• Examination of glucose cycling, insulin/glucose sensitivity, and glycogen supercompensation post-hypoglycemia.

Main Results:

• Glial glycogen can supply the majority of glucose during hypoglycemia for over 100 minutes.
• Brain glycogen concentrations are higher than previously estimated (up to 10 micromol/g).
• Glucose cycling through glycogen is ~1% of cerebral metabolic rate of glucose (CMRglc), ensuring stability.
• Brain glycogen metabolism is sensitive to insulin and glucose levels.
• Hypoglycemic episodes lead to glycogen supercompensation, exceeding pre-hypoglycemia levels.

Conclusions:

• Brain glycogen serves as a vital reserve of glucose equivalents, supporting neuronal function during metabolic stress.
• Evidence supports a role for brain glycogen in diabetes complications, such as impaired glucose sensing and hypoglycemia unawareness.
• Brain glycogen is critical in metabolic states where glucose supply transiently fails to meet demand, including seizures and hypoxia.