Exchange of sulphur against selenium makes insulin analogue last longer

Diabetes mellitus (DM) is caused by either the pancreas not producing enough insulin (Type 1 DM) or the cells of the body not responding properly to the insulin produced (Type 2 DM) resulting in the body’s inability to control blood sugar levels. As a result, diabetics have to consistently monitor their blood glucose concentration, alter their diet and lifestyles, and may have to administer insulin injections to regulate the amount of free sugar in their blood. As of 2015, an estimated 415 million people had diabetes worldwide, with type 2 DM making up about 90% of the cases.


Figure: The structure of insulin. The left side is a space-filling model of the insulin monomer, believed to be biologically active. Carbon is green, hydrogen white, oxygen red, and nitrogen blue. On the right side is a ribbon diagram of the insulin hexamer, believed to be the stored form. A monomer unit is highlighted with the A chain in blue and the B chain in cyan. Yellow denotes disulphide bonds, and magenta spheres are zinc ions.

A group of researchers in Japan has succeeded in synthesizing an  insulin analogue with long-lasting activity by replacing the interchain disulphide in bovine pancreatic insulin (BPIns) with a diselenide bridge. The researchers suggested that the introduction of two juxtaposed selenium atoms to the insulin analogue could lead to a higher kinetic and thermodynamic stability than that of the wild-type without affecting the bioactivity. Indeed,  the synthesized selenoinsulin exhibited  a bioactivity comparable to that of BPIns and its degradation was significantly decelerated (τ_1/2≈8 h vs. ≈1 h for BPIns).