Hagfish insulin: the discrepancy between binding affinity and biologic activity

Area of Science:

• Comparative endocrinology
• Molecular evolution of hormones

Background:

• Insulin is a crucial metabolic hormone with conserved functions across vertebrates.
• Hagfish, as jawless fish, represent an ancient lineage, offering insights into insulin evolution.

Purpose of the Study:

• To investigate the binding characteristics and kinetics of hagfish insulin in mammalian systems.
• To reconcile discrepancies between binding affinity and biologic potency of hagfish insulin.

Main Methods:

• Radioligand binding assays using rat adipocytes and IM-9 lymphocytes.
• Kinetic analysis of insulin-receptor interactions, measuring association and dissociation rates.

Main Results:

• Hagfish insulin showed a binding affinity of approximately 25% relative to pig insulin.
• The biologic potency of hagfish insulin was significantly lower, around 5% in adipocytes.
• Hagfish insulin exhibited slower association and faster dissociation rates compared to pig insulin.

Conclusions:

• The reduced binding affinity and altered kinetics of hagfish insulin contribute to its lower biologic potency.
• Failure to reach steady-state binding in assays may explain previous overestimations of hagfish insulin's binding affinity.