Insulin Overview

Summary

Insulin is a naturally occurring hormone that is administered as a medication in order to treat diabetes mellitus. 

Mechanistically, insulin works by binding to and activating a tyrosine kinase receptor. This causes effects inside the cell that typically work to promote anabolism, or the construction of larger molecules from smaller building blocks. Insulin stimulates glucose transporter 4 or GLUT4 on the surface of cells, which increases glucose uptake from the bloodstream. Insulin also lowers potassium levels in the blood. This may be useful in the treatment of hyperkalemia or high potassium levels, but may in turn cause hypokalemia or low potassium levels as a side effect. Insulin increases glycogen synthesis, protein synthesis, and triglyceride synthesis in different cells of the body. Importantly, insulin does not cross the placenta, so it is safe for use as prescribed during pregnancy.

Side effects of insulin include weight gain and hypoglycemia. In rare cases, fat abnormalities can occur around the injection sites of insulin, manifesting as either lipohypertrophy or lipoatrophy, depending on the specific patient. Lastly, insulin can cause hypersensitivity or allergy in some patients.

Key Points

• Insulin
  • Clinical Use
    • Treats diabetes mellitus
      • Including diabetic ketoacidosis and stress hyperglycemia
      • Treatment depends on type of diabetes
    • Treats hyperkalemia
      • via increase in cellular uptake of potassium
  • Mechanism
    • Binds insulin receptors (tyrosine kinase) to lower blood glucose levels
      • Increase glucose uptake via GLUT4 transporters
        • GLUT4 is found in insulin-dependent tissue (adipose tissue, skeletal muscle)
    • Promotes anabolism via gene transcription
      • Anabolism refers to building of larger complex molecules from smaller builder blocks
      • Increased glycogen synthesis
        • usually occurs in the liver and muscle
      • Increase triglyceride synthesis
        • usually occurs in adipose tissue
      • Increased protein synthesis
        • usually occurs in the liver and muscle
    • Increases uptake of potassium at cell membrane
    • Exogenous insulin (delivered as a drug) does not have C-peptide
      • Endogenous insulin (insulinoma, sulfonylureas) has C-peptide, which is cleaved from insulin in the synthesis process
    • Does not cross placenta
      • Unlike glucose
      • Safe to administer to pregnant mothers
  • Side Effects
    • Hypoglycemia
    • Hypokalemia
    • Weight gain
      • Insulin promotes anabolic metabolism
    • Lipodystrophy (lipohypertrophy or lipoatrophy)
      • Insulin has a direct anabolic effect on local skin leading to fat and protein synthesis. This can cause lipohypertrophy (fat lump) to develop that can also alter drug absorption and dosing
      • An immunogenic reaction can also cause lipoatrophy, although this is more rare
      • Patients are counseled to rotate injection sites to avoid this side effect
    • Allergy/Hypersensitivity
      • Usually a Type 1 (IgE-mediated) hypersensitivity reaction
      • Severity ranges from swelling/erythema/pruritus to a full-on anaphylactic reaction