Fatty acids may influence insulin dynamics through modulation of albumin-Zn2+ interactions
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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.
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
Copyright © 2021 The Authors. BioEssays published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DescriptionWe 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.
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