Diabetes treatment using third generation of insulin: the latest progress in developing new insulin analogs.

Insulin is a key medicine for the management of hyperglycemia in type-1 diabetes andselective individuals with type-2 diabetes. Three different generations of insulin from theoldest to newest are animal insulin, human insulin and insulin analog; the latest has beenrecently developed through mutagenesis in human insulin gene. Three rapid-acting and twolong-acting insulin analogs are currently used for the treatment of diabetes. Although theseanalogs cost more than traditional insulin but they indicate more effective for the patients.The insulin market still demands the new analogs with improved stability andpharmacokinetics. In this direction, we developed a novel strategy in our laboratory for theefficient production of recombinant insulin and its analogs. We introduced a novel expressionand purification system for human insulin, using αB-crystallin (αB-Cry) as the fusion partnerprotein. This system is suitable for directing the synthesis of large amounts of the fusionproteins αB-Cry/A-chain (αB-AC) and αB-Cry/B-chain (αB-BC). After separation of the AandB-chain from their corresponding fusion protein partners, we applied αB-Cry for theefficient folding of human insulin and its analogs. The insulin analogs produced in ourlaboratory indicated improved stability and significantly resist against fibrillation which iscurrently a big medical and biotechnological challenges, while keeping their biologicalactivity to the acceptable levels. We believe that our procedure is also applicable for the largescale production of this highly demanding therapeutic peptide hormone and our new insulinanalogs are potential candidates to be used in treatment of diabetic patients.

Keywords:

Insulin analogs , Diabetes , αB-Crystallin , Insulin folding , Insulin stability