Shu Jie Li

Hyaluronic acid in vivo serves a multitude of functions, including water retention and osmoregulation. Inhibition of hyaluronidase activity prevents the degradation of hyaluronic acid, thereby preserving its normal physiological functions. Fucoidan is a natural sulfated polysaccharide extracted from brown algae. Here, bovine testicular hyaluronidase was separated and purified as a basis for investigating the inhibitory effect of fucoidan on hyaluronidase activity. The experimental results showed that fucoidan exhibited strong competitive inhibition of hyaluronidase activity, with an IC₅₀ value of 4.137 μM. Molecular docking demonstrated that fucoidan binds to the active site of hyaluronidase, with its sulfate groups forming hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations suggested that the complex formed by the binding of fucoidan to hyaluronidase was highly stable, with a binding energy of -24.59 kcal/mol, indicating a high affinity between fucoidan and hyaluronidase. The Ramachandran plot indicated that the binding of fucoidan to hyaluronidase results in a structural change in the active site of the enzyme, making its structure more inert and compact.

Diabetes is characterized by an absolutely inadequate insulin secretion (type 1 diabetes mellitus) or a relative deficit in insulin secretion due to insulin resistance (type 2 diabetes mellitus), both of which result in elevated blood glucose. Understanding the molecular mechanisms underlying the pathophysiology of diabetes could lead to the development of new therapeutic approaches. The voltage-gated proton channel Hv1 is an ion channel with specific selectivity for protons, which is regulated by membrane potential and intracellular pH. Recently, our studies showed that Hv1 is expressed in β cells of the endocrine pancreas. Knockout of Hv1 reduces insulin secretion and results in hyperglycemia and glucose intolerance, but not insulin resistance. Furthermore, knockout of Hv1 leads to diet-induced obesity due to inflammation and hepatic steatosis. Increasing evidence suggests that Hv1 plays a pivotal role in glucose homeostasis and lipid metabolism. This review aims to summarize advances made so far in our understanding of the roles of Hv1 in the regulation of insulin secretion in β cells, glucose homeostasis, and obesity.