• Clinical science

Insulin

Abstract

Insulin is an anabolic peptide hormone that is produced and secreted from beta cells located in the islets of Langerhans of the pancreas. It has important metabolic functions, which include promoting the storage of carbohydrates, amino acids, and fat in the liver, skeletal muscle, and adipose tissues. By modulating glucose absorption from the blood, insulin lowers blood glucose levels. Insulin therapy is an important part of treatment for individuals with insufficient or absent insulin production (e.g., diabetes mellitus, gestational diabetes). Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure and differ in onset, peak, and duration compared to human insulin. It is crucial that patients receiving insulin therapy undergo in-depth training to prevent potentially life-threatening conditions such as hypoglycemia as a result of an insulin overdose or drug interactions.

For further information on insulin therapy and regimens, see insulin therapy.

Overview

Types of insulinand trade names Effect Application Special features
Rapid-acting insulin
Insulin lispro
  • Onset: 5–30 min
  • Peak: 30 min–3 h
  • Duration: 3–5 h
  • Injected before a meal time
  • Used in combination with longer-acting insulin
Insulin aspart
Insulin glulisine
Short-acting insulin
Regular insulin
  • Onset: ∼30 min
  • Peak: 2.5–5 h
  • Duration: 4–24 h
  • Mandatory interval between injections and meal times: ∼30 min
  • Used in combination with longer-acting insulin
  • Intravenous therapy available (only for this type of insulin)
Intermediate-acting insulin
NPH insulin
  • Onset: 1–2 h
  • Peak: 4–12 h
  • Duration: 14–24 h
  • Crystalline suspension consisting of regular insulin (with a high level of solubility) and protamine (with a low level of solubility)
  • Mandatory interval between injections and meal times: 30–60 min
  • Used in combination with rapid or short-acting insulin
  • Usually administered twice daily
Long-acting insulin
Insulin glargine
  • Onset: 1.5–4 h
  • Peak: flat; not defined
  • Duration: ∼ 24 h
  • Insulin analogs
  • More consistent efficacy profile and longer duration of effect compared to NPH insulin due to different modes of action
    • Glargine: formation of precipitates that slowly dissolve at the injection site
    • Detemir: interaction with serum albumin
    • Degludec: formation of slowly dissolving multi-hexamers
  • Used in combination with rapid or short-acting insulin
  • Administered once or twice daily
Insulin detemir
Insulin degludec
Ultralente insulin
Mixed insulin
Mixed insulin
  • Contains regular insulin and NPH insulin mixed according to a defined ratio
  • Example: Actraphane® 30/70, contains 30% regular insulin and 70% NPH insulin
  • Some manufacturers only add one number to the trade name, e.g., Insuman® Comb 25
  • Administered two or three times a day

Some manufacturers use the same trade name for both regular insulin and mixed insulin (with a varying amount of NPH insulin). The package insert should be read carefully!

Effects

  • Insulin is an anabolic peptide hormone; that is produced and secreted from beta cells in the islets of Langerhans of the pancreas in response to a rise in blood glucose
  • Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure; after injection they exert the same actions but differ in onset, peak and duration compared to human insulin
  • Insulin binds to insulin receptors (a type of tyrosine kinase receptor) located in various tissues in the body (e.g., liver, skeletal muscle, adipose tissue) and has the following actions:
Increases Decreases
Carbohydrate metabolism
  • Uptake of glucose into cell
  • Glycogenesis
  • Glycolysis
Lipid metabolism
  • Lipid synthesis
Protein metabolism
  • Proteolysis
Other effects
  • Secretion of gastric acid
  • Cell growth and differentiation
  • Uptake of potassium

References:[1][2]

Side effects

We list the most important adverse effects. The selection is not exhaustive.

Indications

Interactions

Insulin demand Drug
Increased
Decreased
Either increased or decreased

Pharmacokinetics

  • Absorption: The absorption time determines the onset, peak, and duration of effect.
  • Prolonged absorption time
    • Low temperature
    • Obesity
    • Peripheral injection site
    • Superficial subcutaneous injection
  • Shorter absorption time
    • Manipulative therapy (e.g., massages)
    • Deep subcutaneous injection
    • Injection into the abdominal skin around the navel
  • 1. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • 2. Mantzoros C, Serdy S, Nathan DM, Mulder JE. Insulin Action. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/insulin-action. Last updated September 7, 2016. Accessed June 13, 2018.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
last updated 11/11/2018
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