Fatty acids may influence insulin dynamics through modulation of albumin‐Zn2+ interactions. (1st November 2021)

• Record Type: Journal Article
• Authors: Arya, Swati; Gourley, Adam J.; Penedo, J. Carlos; Blindauer, Claudia A.; Stewart, Alan J.
• Is Part Of: BioEssays. Volume 43:Number 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-01
• Subjects: diabetes -- Förster resonance energy transfer -- insulin decomplexation -- insulin resistance -- non‐esterified fatty acids -- serum albumin -- zinc; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202100172
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Insulin is stored within the pancreas in an inactive Zn 2+ ‐bound hexameric form prior to release. Similarly, clinical insulins contain Zn 2+ and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn 2+ disengages from the complex. In plasma and other extracellular fluids, the majority of Zn 2+ is bound to human serum albumin (HSA), which plays a vital role in controlling insulin pharmacodynamics by enabling removal of Zn 2+ . The Zn 2+ ‐binding properties of HSA are attenuated by non‐esterified fatty acids (NEFAs) also transported by HSA. Elevated NEFA concentrations are associated with obesity and type 2 diabetes. Here we present the hypothesis that higher NEFA levels in obese and/or diabetic individuals may contribute to insulin resistance and affect therapeutic insulin dose‐response profiles, through modulation of HSA/Zn 2+ dynamics. We envisage this novel concept to have important implications for personalized treatments and management of diabetes‐related conditions in the future. Abstract : Insulins exist in a Zn 2+ ‐bound hexameric form and only become active once Zn 2+ dissociates. Albumin has been proposed to facilitate sequestration of Zn 2+ from insulin. Plasma fatty acids, which are elevated in metabolic disease states, perturb albumin's ability to bind Zn 2+ and may contribute to altered insulin dynamics in diabetes.