Insulin is a hormone crucial to the regulation of glucose metabolism. In humans, the monomer of human insulin (HI) is active and may be stored as inactive hexamers. HI is known to aggregate into hexamers when in the presence of various cations and conformation changes are induced by anionic and phenolic allosteric effector molecules. While the mechanism of aggregation is poorly understood, analysis of surface behavior at the air-water interface can be used to study aggregation under various conditions. To this end, the Langmuir monolayer technique was employed to model HI aggregation in the presence of zinc, copper, and vanadium ions. Comparison of surface pressure-area isotherms indicate measurable differences in aggregation of surface HI, dependent upon the present ion. Both zinc and copper ions were found to induce hexamer aggregation of surface HI with consistent isotherm differences between the two ions. Whether surface HI would aggregate into hexamers was determined by the oxidation state of vanadium. Isotherms of the +4-oxidation state were found to share compression similarities with zinc and copper suggesting hexamer formation. The +5-oxidation state isotherms shared similarities with monomeric HI compression isotherms strongly suggesting monomer presence.

Effects of various metal cations on the aggregation of human insulin Langmuir monolayers

ACS Spring Meeting 2021

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