Physiology · Endocrine System

Insulin secretion, actions and regulation of glucose homeostasis

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Definition

  • Insulin is an anabolic peptide hormone from pancreatic β cells (A chain 21 aa, B chain 30 aa, disulfide-linked).
  • It is the only glucose-lowering and only anti-ketogenic hormone.

Structure, Synthesis and β-Cell Secretory Products

Products of the β-cell granule

  • Insulin: about 95%.
  • Proinsulin: about 3%, about 10% bioactivity.
  • C peptide: about 7%, no bioactivity.
  • Proinsulin and C peptide are secreted in equimolar ratio with insulin.

Steps of synthesis

  1. Insulin is synthesized as preproinsulin (110 amino acids).
  2. Its N-terminal signal peptide is cleaved to form proinsulin (86 amino acids: B chain, C peptide, A chain in sequence).
  3. Proinsulin enters the Golgi, where disulfide bridges fold it.
  4. Folded proinsulin is cleaved to insulin plus C peptide.
  5. The products are packaged with zinc into secretory granules.