Insulin glulisine

Insulin glulisine is a rapid-acting modified form of medical insulin that differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. It was developed by Sanofi-Aventis and approved for marketing by the FDA and the EMA in 2004; it is sold under the trade name Apidra. When injected subcutaneously, it appears in the blood earlier than regular human insulin (RHI). When used as a meal time insulin, the dose is to be administered within 15 minutes before or 20 minutes after starting a meal. Intravenous injections may also be used for extreme hyperglycemia, but must be performed under the supervision of a medical professional.

The most common side effects include hypoglycaemia (low blood glucose levels).

Medical uses
Insulin glulisine is indicated for the treatment of diabetes mellitus.

Mechanism behind the rapid bioavailability
The monomer-monomer interactions are weaker in insulin glulisin compared to unmodified human insulin, and therefore, it does not as readily form dimers and hexamers, which are dominant in unmodified insulin. Due to their large size, insulin hexamers need to break up into dimers or monomers before they are able to enter the blood and become biologically active. Specifically, the B3 mutation causes electrostatic repulsion in the hexamer to arginine-22 in the B chain of other insulin molecules in the same hexamer, while the B29 mutation causes fewer hydrogen bonds to stabilize the dimer. Furthermore, the isoelectric point of insulin glulisine insulin, which is shifted from 5.5 (of unmodified human insulin) to 5.1, increases the solubility at physiological pH levels.