| Response | Glucose Threshold | Role |
| ↓ insulin | 80–85 mg/dL | First defense |
| ↑ glucagon | 65–70 mg/dL | Second defense |
| ↑ epinephrine | 65–70 mg/dL | Third defense: critical when glucagon is deficient |
| ↑ cortisol & growth hormone | 65–70 mg/dL | Involved: not critical (slow, hours to days) |
| symptoms | 50–55 mg/dL | Prompts behavioral defense (hunger) |
| cognition | < 50 mg/dL | (compromises behavioral defense) |
Although the adult human brain constitutes only about 2.5% of body weight, its oxidative metabolism accounts for approximately 25% of the basal metabolic rate and more than 50% of whole-body glucose utilization. The brain can utilize alternative fuels if their circulating levels rise high enough for them to enter the brain in quantity.
For example, during extended fasting, markedly elevated circulating ketone levels can support the majority of the energy needs of the brain and reduce its utilization of glucose. Nonetheless, that is not a physiologic condition.
Furthermore, ketogenesis is suppressed during episodes of insulin-mediated hypoglycemia. Again, the brain is critically dependent on a virtually continuous supply of glucose from the circulation.