Understanding the structure and function of cone snail insulin as a substitute for human insulin

Abstract

It is estimated that more than 415 million people currently have diabetes. Diabetes is an inability to properly regulate and/or produce insulin. Insulin dependent diabetics need to inject themselves with insulin in order to eat, drink, and function properly. Current insulin activation is around fifteen minutes but can take up to 90 minutes to fully activate. Cone snail insulin (CSI) appears to have the ability to fully activate within minutes. Rapid activation can prevent the body from spending long periods of time in a hyperglycemic state (too much sugar in the bloodstream). Long periods of time in a hyperglycemic state can cause damage to blood vessels and nerves, which in turn, leads to damage to the entire body. The goal of this research process was to discover why and how CSI binds to the receptors and how to mimic this behavior to decrease the activation time of insulin in the human body. The exploration phase of this research inquired how CSI would potentially bind with human insulin receptors and determine if it would be possible to mimic this to use in diabetic patients to decrease the activation time. During the modeling phase of this project, JMOL was used to compare the molecular structures and functions of CSI and human insulin in order to establish if CSI would be interchangeable with human insulin. Cone snail venom contains insulin which causes a hypoglycemic sedation, paralyzing its victim on contact. While researching this process, it was discovered that the B‐chain on the CSI protein is missing the amino acid residues from B23–B30. Human insulin, when stored in the pancreas, aggregates into dimers. These dimers group together to form hexamers. Injected insulin is also in dimer form, but it needs to disaggregate in order to become effective. One human insulin molecule binds to the other using hydrogen bonds on the amino acid residues from B23–B30. Because CSI is missing this portion, it can enter the bloodstream without aggregating. In order to mimic the function of the CSI in humans, human insulin needs to be modified to eliminate the aggregation of insulin cells in the human body. To do this the Mahtomedi High School team, Mahtomedase, MSOE Center for BioMolecular Modeling MAPS Team used 3D modeling and printing technology to examine structure‐function relationships between CSI and human insulin. Current insulin activation time can take, at minimum, fifteen minutes. CSI has the potential to increase reaction time by upwards of 200 percent by more readily binding to the human insulin receptor.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.