FAST ACTING INSULIN

One of the most important development in diabetes has been the use of genetic engineering to make insulin preparations that work faster than regular insulin. (If you have begun using insulin in the past few years you are probably using an insulin like this one.) The diagram compares the serum insulin levels following injection of each type of insulin. (The graphs covers ten hours.)

(adapted from Diabetes Care 22:1501-6 (1999))

The main use of the fast acting insulin is to permit injections when a meal begins. Regular insulin is best when injected a half hour or so before eating.

The science making such tailoring of insulin action possible is well understood. The reason this is possible is that natural insulin forms aggregates but can only function as a hormone when the aggregates come apart into individual insulin molecules. When stored in a concentration solution insulin naturally forms hexamers made of six insulin molecules and six zinc ions:

After injection the hexamer gradually disassociates into insulin because the insulin is much more dilute:

By changing an amino acid at the interface (example above: amino acid B28 is changed from proline to aspartic acid), the insulin molecules are much less attracted to each other and the hexamer falls apart quickly. The result is quicker biological action.