Insulin Pharmacology
Mechanisms · Preparations · Dosing · Adverse Effects
Beta Cell Glucose-Stimulated Insulin Secretion
Glucose enters via GLUT-2
→
Glucokinase metabolizes glucose
→
ATP/ADP ratio rises
→
K-ATP channel closes
→
Membrane depolarizes
→
Ca² influx → Insulin secreted
Sulfonylureas close K-ATP channels independent of glucose — same downstream effect, hence hypoglycemia risk.
Insulin Preparations: Pharmacokinetic Profiles
Class Examples Onset Peak Duration / Notes
Rapid Lispro, aspart, glulisine 10–15 min 1–2 hr 3–5 hr; inject at mealtime
Short Regular insulin 30–60 min 2–3 hr 5–8 hr; only IV-safe insulin
Intermediate NPH (neutral protamine Hagedorn) 1–2 hr 4–8 hr 12–18 hr; nocturnal hypoglycemia risk
Long Glargine, detemir, degludec 1–2 hr Peakless 20–42 hr; once-daily basal coverage
Receptor Signaling: Key Downstream Effects
  • Muscle & fat: GLUT-4 vesicle translocation → glucose uptake
  • Liver: glycogen synthesis up, gluconeogenesis suppressed
  • Fat: lipolysis inhibited, free fatty acid release reduced
  • All tissues: amino acid and potassium uptake promoted
Adverse Effects & Interactions
  • Hypoglycemia: most dangerous adverse effect; rule of 15 for treatment
  • Weight gain 2–6 kg with intensification
  • Lipohypertrophy at injection sites → erratic absorption
  • Beta-blockers: mask tachycardia, prolong hypoglycemia
  • Glucocorticoids: increase requirements, afternoon glucose most affected
  • Alcohol: inhibits gluconeogenesis, delayed hypoglycemia risk
Clinical Pearls
Pregnancy Insulin is the only proven-safe antihyperglycemic agent. Does not cross placenta. Lispro and aspart preferred rapid-acting agents. Requirements double by third trimester, fall abruptly post-delivery.
Critical Care / Perioperative Target glucose 140–180 mg/dL. Basal at 75–80% of usual dose; bolus held while fasting. Intravenous regular insulin for major surgery or intensive care unit. NICE-SUGAR: intensive control (81–108) increased mortality.
Renal Impairment Reduced insulin clearance prolongs action. Dose reduction required as estimated glomerular filtration rate falls below 30 mL/min. Hypoglycemia risk increases significantly.