Dr M.A. Islam (pictured) and Prof T.S. Pillay  from the Department of Chemical Pathology have determined how inherited mutations in the insulin gene lead to defective binding to the insulin receptor and result in diabetes mellitus. The research, which was a collaboration with scientists at the College of Health Sciences, UKZN (Dr A.Adeniyi and Prof M. Soliman, Discipline of Pharmaceutical Sciences)  has just  been published in the Journal of Biomolecular Structure and Dynamics. Dr Islam was funded by the UP Vice Chancellors Postdoctoral Fellowship.

There are 3 inherited mutations in the insulin gene referred to as insulins Wakayama, Los Angeles and Chicago after the cities in which they were discovered. The mutations result from single amino acid substitutions.  These result in the production of defective insulin molecules with altered biological properties and the development of diabetes mellitus in the affected families. The research defines at the molecular level how the mutations affect the contact points in the receptor much like the way a defective key can fail to open a lock. This work is the first description worldwide  of how these defective molecules bind to the insulin receptor paving the way to a better understanding and the development of new analogs that can be used to activate the insulin receptor and treat diabetes mellitus. 

Structures of normal and mutant insulins Wakayama, Los Angeles and Chicago