Human Serum Albumin Structure in Presence of Different Concentrations of Cortisol and Glucose: An In Vitro Modeling Under Normal and Hyperglycemic Conditions

Glucose is an essential element in the supply of body’s energy. In diseases such as diabetes, glucose increase is associated with disturbance in metabolism. Cortisol is an important hormone in the regulation of glucose metabolism, and human serum albumin (HSA) is one of the most important glucose and cortisol transmitters in blood. Interaction between albumin and these ligands could affect HSA secondary structure and its stability.
The aim of this study was to investigate HSA secondary structure in the presence of different concentrations of glucose and cortisol.
This was an in vitro (analytical/descriptive) study in which, completely randomized design was used to study the interaction between human serum albumin at 37°C at different glucose concentrations of 0, 80, 180, 240, and 400 mg/dL and cortisol at concentrations of 0, 10, 20, and 40 µg/dL. Intrinsic fluorescence spectroscopy and Circular dichroism (CD) were performed to obtain data.
HSA secondary structure underwent changes in the presence of different concentrations of cortisol and glucose. P values less than 0.01 were considered to be statistically significant. Fluorescence spectroscopy and CD results showed that at normal glucose concentrations, HSA was very flexible, beta-sheet content reduced, and the maximum increase in fluorescence and blue-shift happened. At higher concentrations of glucose, HSA became rigid. Also, HSA in presence of 10 µg/dL cortisol was very flexible; but a cortisol concentration of 40 µg/dL caused stability in HSA structure in presence of different glucose concentrations.
Under normal glucose conditions, very low cortisol concentrations create large changes in HSA secondary structure. At normal glucose concentrations, some of the binding sites of HSA that are all occupied by glucose at higher concentrations become available to cortisol. Cortisol structure is very hydrophobic, which causes large changes in HSA secondary structure and significant increases in quenching and blue shift. In conclusion, binding of compounds such as medicines to HSA sites may be affected by competitive bindings of glucose, depending on its concentration in the blood.