Insulin: Hormonal Regulation of Blood Glucose

Insulin — anabolic peptide hormone from pancreatic β-cells — is the primary regulator of glucose homeostasis.

Physiologic Sequence

1. Meal → Glucose absorption → portal vein → pancreas
2. β-cell sensing: Glucose → GLUT2 → glycolysis → ATP/ADP ratio ↑ → K_ATP channel closure → depolarization → Ca²⁺ influx → insulin granule exocytosis
3. Insulin action: Binds receptor tyrosine kinase (IR) → IRS/PI3K/Akt pathway → GLUT4 translocation (muscle, fat) → glucose uptake
4. Hepatic effects: Glycogen synthesis, glycolysis ↑; gluconeogenesis, glycogenolysis ↓
5. Lipid/protein: Lipogenesis ↑, lipolysis ↓; protein synthesis ↑

Pathophysiology

• Type 1 DM: Autoimmune β-cell destruction → absolute insulin deficiency
• Type 2 DM: Insulin resistance + relative deficiency
• Insulin resistance: Impaired signaling → compensatory hyperinsulinemia → eventual β-cell failure

Therapeutic Insulin

• Rapid-acting (lispro, aspart, glulisine)
• Short-acting (regular)
• Intermediate (NPH)
• Long-acting (glargine, detemir, degludec)
• Pre-mixed

Goal: mimic physiologic pattern (basal + prandial).