Short-Acting and Rapid-Acting Insulin

Frequently asked questions

What chemical modifications distinguish insulin aspart and glulisine from human insulin?

Insulin aspart and insulin glulisine are created using chemical modification principles similar to insulin lispro.

• Prevention of aggregation — structural changes prevent the formation of dimers and hexamers.
• As a result of chemical modification, these preparations remain in monomeric form, ensuring faster absorption compared to regular human insulin.

What is the mechanism of action of insulin at the cellular level?

The mechanism of insulin action is based on the activation of specific membrane receptors with tyrosine kinase activity.

• Binding — the hormone interacts with the extracellular $\alpha$-subunits of the receptor.
• Activation — transmembrane $\beta$-subunits approximate and undergo autophosphorylation at tyrosine residues.
• Signaling cascade — insulin receptor substrate-1 (IRS-1) is phosphorylated, binds to PI3 kinase, leading to $PIP_3$ production and protein kinase B activation.
• Effects — the complex undergoes endocytosis. Translocation of GLUT-4 transporters to the membrane occurs for glucose uptake, along with the activation of glycolysis and glycogen synthase enzymes, and the inhibition of glycogenolysis.

What are the possible adverse effects of insulin therapy besides hypoglycemia?

In addition to hypoglycemia, insulin therapy can cause local and immune adverse reactions.

• Allergic reactions — can occur against the preparation itself (especially with animal insulins due to protein impurities such as proinsulin or C-peptide).
• Lipodystrophy — local disruption of adipose tissue at injection sites (post-injection lipodystrophy), resulting from repeated administration into the same area.

What are the acceptable routes of administration for short-acting and rapid-acting insulins?

Short-acting and rapid-acting insulins are administered exclusively via parenteral routes.

• Subcutaneous administration — the primary route for systematic treatment and control of postprandial glycemia (administered before meals).
• Intravenous administration — permissible for short-acting and rapid-acting preparations when managing emergencies (e.g., diabetic ketoacidosis/coma).
• Intramuscular administration — mentioned as a possible parenteral route for insulin preparations.

Oral administration is impossible due to the destruction of the hormone by gastrointestinal enzymes.

In which emergency conditions is intravenous administration of short-acting insulin indicated?

Intravenous administration of short-acting insulin is indicated in life-threatening conditions for rapid therapeutic effect.

• Diabetic ketoacidosis (DKA) — for emergency correction of hyperglycemia and metabolic acidosis.
• Diabetic coma — for rapid management of acute carbohydrate metabolism decompensation.
• Severe hyperkalemia — in chronic kidney disease, insulin is administered IV as a bolus (combined with $\beta_2$-agonist nebulization) to rapidly lower blood potassium levels and treat life-threatening arrhythmias.

What is the main pharmacokinetic difference between insulin lispro and regular human insulin?

Due to chemical modification, insulin lispro does not form dimers and hexamers. It exists in a monomeric form, allowing it to be absorbed twice as fast (onset within 15 minutes) with a short duration of action of up to 3 hours.

Which drug classes enhance the hypoglycemic effect of insulin?

Sulfonamides, anabolic steroids, MAO inhibitors, and $\beta$-blockers enhance the hypoglycemic action; $\beta$-blockers can additionally mask the symptoms of hypoglycemia.

What are the main formulations and pharmacokinetics of Regular human insulin (e.g., Actrapid HM)?

Regular insulin is available in vials of 40 or 100 IU/mL, as well as in cartridges for insulin pens. Its onset of action occurs in 30 minutes, peaking at 1–3 hours, with a total duration of about 8 hours.