Molecular Structure
Chemically, insulin is a polypeptide. The mature active hormone molecule consists of two polypeptide chains:
- A-chain: Contains 21 amino acid residues.
- B-chain: Consists of 30 amino acid residues.
The spatial structure of the hormone is stabilized by three disulfide bonds. Two of these are interchain bonds (firmly linking the A-chain to the B-chain). The third bond is an intrachain bond, forming a loop within the A-chain itself.
Biosynthesis and Secretion Stages
Insulin production is a complex multi-step process occurring in the pancreatic $\beta$-cells:
- Translation and preproinsulin formation. Polypeptide chain synthesis begins on polyribosomes attached to the rough endoplasmic reticulum (RER). This produces an inactive precursor containing a signal peptide.
- Proinsulin formation. Within the lumen of the RER, the signal peptide is cleaved off, and the molecule folds with the formation of disulfide bonds, yielding proinsulin.
- Processing in the Golgi apparatus. Proinsulin is transported to the Golgi apparatus, where specific proteases excise the connecting segment known as the C-peptide.
- Packaging. Mature insulin (A and B chains) and C-peptide are packaged into secretory granules.
- Exocytosis. Upon stimulation, granule contents are released into the extracellular space.
Regulation of Production and Metabolism
The primary stimulus for insulin secretion is an elevated blood glucose concentration (hyperglycemia). Additional stimuli include amino acids (particularly arginine and lysine), fatty acids, and ketone bodies. Hormone production is inhibited by epinephrine, somatostatin, and certain gastrointestinal peptides.
After performing its function, the hormone degrades rapidly, with a half-life of only 3–10 minutes. Cleavage is catalyzed by the enzyme insulin-degrading enzyme, which is localized predominantly in the liver and to a lesser extent in the kidneys.
Mechanism of Action and Metabolic Effects
The insulin signal is transmitted via a specific tyrosine kinase receptor on the membrane of target cells (liver, muscle, adipose tissue). Hormone binding induces phosphorylation of intracellular insulin receptor substrate (IRS) proteins, triggering the PI3K/Akt and MAPK signaling cascades.
- Anabolism is activated in tissues as a result:
- Glucose transport into cells increases due to the translocation of GLUT4 transporters to the membrane.
- Glycolysis and glycogen synthesis are stimulated.
- Lipogenesis (fat formation) and protein synthesis are enhanced.
Clinical Significance of C-Peptide
C-peptide is secreted into the bloodstream in a strict equimolar ratio with insulin (1:1). However, its half-life is significantly longer—approximately 30 minutes.
In laboratory diagnostics, C-peptide levels are used to assess endogenous pancreatic insulin secretion. This is especially important if the patient is already receiving exogenous insulin injections (pharmaceutical preparations do not contain C-peptide, so the assay reflects only what the body's own pancreas has produced).