Canine Diabetes Wiki
Humulin n

Humulin N, an isophane insulin suspended with protamine.

Protamines are proteins derived from the sperm or testes of salmon or related fish. They are added [1] are added to insulins NPH Neutral Protamine Hagedorn and PZI protamine zinc to delay their absorption.

The difference between isophane/NPH insulins and PZI insulins is the amount of protamine used; there is more in PZI than in NPH/isophane insulins. It's the extra protamine which makes the PZI a slow-acting insulin.[2]

The basis of absorption of any insulins containing protamine [3] is the breakdown of this protein by proteolytic enzymes [4] or proteases in the body. Only after this is accomplished can the insulin itself be absorbed. More protamine in the suspension means insulin absorption will be delayed longer; less protamine means the insulin will act faster.

Protamine, like insulin itself, is a protein. In the case of antibody formation, it is possible that the insulin itself is not the cause of them; the proteins present in the suspension, such as protamine, may be. [5] In this case, changing the type of suspension would solve the problem.

Protamine has other medical uses as well.

See also suspension. I16


  1. The Diagnosis and Management of Anaphylaxis - Protamine. Journal Allergy & Clinical Immunology (1998).
  2. Greco, Deborah (2010). Treating Diabetes Mellitus in Dogs and Cats. Western Veterinary Conference.
  3. Williams, Robert (1968). Textbook of Endocrinology, 4th edition. W. B. Saunders.
  4. Proteolytic Enzymes. Wikipedia.
  5. Problems With Regulation of Diabetes Mellitus-Antibodies. Intervet.