Fed and fasting states: glucose counter-regulation and ketogenesis
How the insulin to glucagon ratio switches the body between storage and mobilisation, the phases of fasting and the protein-sparing shift to ketones, the glycaemic thresholds for counter-regulation, the biochemistry of hepatic ketogenesis, and how these explain DKA, euglycaemic and alcoholic ketoacidosis, starvation ketosis and hypoketotic hypoglycaemia.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- The insulin to glucagon ratio, sensed mostly by the liver through the portal vein, decides whether the body is storing or releasing fuel.
- Fasting runs in phases: glycogenolysis (first 24 hours), gluconeogenesis (days 1 to 3), then ketone adaptation that spares protein.
- Ketogenesis needs two things together: low insulin (to free fatty acids from fat) and high glucagon (to open CPT1 in the liver). Lose either and ketones stay low.
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Sources
- Williams Textbook of Endocrinology, 15th editionElsevier (Melmed S, Auchus RJ, Goldfine AB, Rosen CJ, Kopp PA, editors), 2024
- Lehninger Principles of Biochemistry, 8th editionMacmillan Learning (Nelson DL, Cox MM), 2021
- Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr 2006;26:1-22Annual Review of Nutrition, 2006
- Cryer PE, Axelrod L, Grossman AB et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2009;94:709-28Endocrine Society, 2009
- Umpierrez GE, Davis GM, ElSayed NA et al. Hyperglycemic crises in adults with diabetes: a consensus report. Diabetes Care 2024;47:1257-75ADA, EASD, JBDS, AACE and Diabetes Technology Society, 2024
- Last updated
- 14 November 2026
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