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C-termini of B chains. Additionally, in the presence of zinc ions, insulin dimers associate into
hexamers.
These interactions have important clinical ramifications. Monomers and dimers readily diffuse into
blood, whereas hexamers diffuse poorly. Hence, absorption of insulin preparations containing a high
proportion of hexamers is delayed and somewhat slow. This phenomenon, among others, has
stimulated development of a number of recombinant insulin analogs. The first of these molecules to
be marketed - called insulin lispro - is engineered such that lysine and proline residues on the C-
terminal end of the B chain are reversed; this modification does not alter receptor binding, but
minimizes the tendency to form dimers and hexamers.