Fatty acids may influence insulin dynamics through modulation of albumin-Zn2+ interactions
Abstract
Insulin is stored within the pancreas in an inactive Zn2+-bound hexameric form prior to release. Similarly, clinical insulins contain Zn2+ and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn2+ disengages from the complex. In plasma and other extracellular fluids, the majority of Zn2+ is bound to human serum albumin (HSA), which plays a vital role in controlling insulin pharmacodynamics by enabling removal of Zn2+. The Zn2+-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/Zn2+ dynamics. We envisage this novel concept to have important implications for personalised treatments and management of diabetes-related conditions in the future.
Citation
Arya , S , Gourley , A J , Penedo , J C , Blindauer , C A & Stewart , A J 2021 , ' Fatty acids may influence insulin dynamics through modulation of albumin-Zn 2+ interactions ' , BioEssays , vol. 43 , no. 12 , 202100172 . https://doi.org/10.1002/bies.202100172
Publication
BioEssays
Status
Peer reviewed
ISSN
0265-9247Type
Journal article
Description
We thank the Leverhulme Trust (grant no. RPG-2017-214), the Scottish Funding Council (through a St Andrews Restarting Research Fund award) and the Wellcome Trust (through an Institutional Strategic Support Fund award; grant no. 204821/Z/16/Z) for funding.Collections
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