HbA1c and insulin: the pathway in the body

This page shows the biochemical pathway behind the laboratory value HbA1c: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

HbA1c is haemoglobin to which glucose has become firmly attached without an enzyme. Because red blood cells circulate for several weeks, its share reflects the glucose level over that time; insulin controls how much glucose cells absorb.

The pathway step by step

1. Carbohydrates → Glucose in blood Digestive enzymes From the gut, glucose travels in the blood to all tissues. The liver also releases or absorbs glucose, smoothing out the swings between meals. Source 7
2. Glucose in blood → Insulin Glucokinase · ATP Beta cells of the pancreas absorb glucose. Glucokinase converts it; the more ATP this produces, the more insulin the cells release. Source 4
3. Insulin → Insulin receptor Insulin binds to its receptor from the outside. The receptor is itself an enzyme: it attaches phosphate groups to itself and to proteins inside the cell, passing the signal on. Source 5
4. Insulin receptor → GLUT4 in the membrane PI3K, Akt · ATP Via the PI3K and Akt signalling chain, vesicles carrying the transporter GLUT4 move to the cell surface. Only then can glucose flow into muscle and fat cells. Source 6, 5
5. GLUT4 in the membrane → Glucose in the cell Hexokinase · ATP Inside the cell, hexokinase immediately attaches a phosphate group. The glucose is then either assembled into glycogen or broken down in glycolysis. Source 7
6. Glucose in red cells → Schiff base no enzyme Glucose attaches to an amino group of haemoglobin without any enzyme. This first bond, called an aldimine or Schiff base, is loose and easily comes apart again. Source 1
7. Schiff base → HbA1c Amadori rearrangement Part of the loose compound slowly rearranges (Amadori rearrangement) and becomes fixed. This form is called HbA1c. It no longer comes apart but stays on the haemoglobin. Source 1, 2
8. HbA1c → Breakdown in the spleen Red blood cells are broken down after a number of weeks, and the bound HbA1c with them. Its share in the blood therefore reflects the period in which the cells were in circulation. Source 3

Cofactors in this pathway

• Zinc — Two zinc ions hold six insulin molecules together in the storage granules of the beta cell Source 8In the ORY catalogue as a laboratory value: Zink
• Magnesium — Accompanies ATP in kinases such as glucokinase and the insulin receptor Source 9In the ORY catalogue as a laboratory value: Magnesium
• Potassium — When the ATP-dependent potassium channels of the beta cell close, insulin release begins Source 4In the ORY catalogue as a laboratory value: Kalium (intrazellulär)
• Calcium — Flows into the beta cell and triggers the release of insulin granules Source 4In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• ATP — Formed as the beta cell breaks down glucose, and closes its potassium channels Source 4

Sources

1. Bunn HF, Higgins PJ. Reaction of monosaccharides with proteins: possible evolutionary significance. Science 1981 · PubMed 12192669
2. Shin A, Connolly S et al. Protein glycation in diabetes mellitus. Adv Clin Chem 2023 · PubMed 36858645
3. Xu Y, Bergenstal RM et al. Addressing shortfalls of laboratory HbA(1c) using a model that incorporates red cell lifespan. Elife 2021 · PubMed 34515636
4. Rorsman P, Ashcroft FM. Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men. Physiol Rev 2018 · PubMed 29212789
5. Saltiel AR. Insulin signaling in health and disease. J Clin Invest 2021 · PubMed 33393497
6. Klip A, McGraw TE et al. Thirty sweet years of GLUT4. J Biol Chem 2019 · PubMed 31175156
7. Rui L. Energy metabolism in the liver. Compr Physiol 2014 · PubMed 24692138
8. Li YV. Zinc and insulin in pancreatic beta-cells. Endocrine 2014 · PubMed 23979673
9. de Sousa Melo SR, Dos Santos LR, da Cunha Soares T et al. Participation of Magnesium in the Secretion and Signaling Pathways of Insulin: an Updated Review. Biol Trace Elem Res 2022 · PubMed 35666386

Related pathways

• Iron and ferritin — haemoglobin
• Vitamin D — Zink, Magnesium
• Calprotectin — Zink, Calcium (intrazellulär)
• Estradiol — Zink, Magnesium
• GABA, glutamate and glutamine — Magnesium, Kalium (intrazellulär)

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
Legal notice Privacy policy All biomarkers