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Fatty acids may influence insulin dynamics through modulation of albumin‐Zn2+ interactions
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Arya, Swati, Gourley, Adam J., Penedo, J. Carlos, Blindauer, Claudia A. and Stewart, Alan J. (2021) Fatty acids may influence insulin dynamics through modulation of albumin‐Zn2+ interactions. BioEssays, 43 (12). 2100172. doi:10.1002/bies.202100172 ISSN 0265-9247.
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WRAP-Fatty-acids-insulin-dynamics-modulation-albumin‐Zn2-interactions-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (828Kb) | Preview |
Official URL: https://doi.org/10.1002/bies.202100172
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 personalized treatments and management of diabetes-related conditions in the future.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Insulin resistance, Fatty acids, Zinc in the body, Diabetes -- Complications | ||||||||||||
| Journal or Publication Title: | BioEssays | ||||||||||||
| Publisher: | John Wiley & Sons Ltd. | ||||||||||||
| ISSN: | 0265-9247 | ||||||||||||
| Official Date: | December 2021 | ||||||||||||
| Dates: |
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| Volume: | 43 | ||||||||||||
| Number: | 12 | ||||||||||||
| Article Number: | 2100172 | ||||||||||||
| DOI: | 10.1002/bies.202100172 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
| Copyright Holders: | © 2021 The Authors. BioEssays published by Wiley Periodicals LLC | ||||||||||||
| Date of first compliant deposit: | 29 June 2022 | ||||||||||||
| Date of first compliant Open Access: | 29 June 2022 | ||||||||||||
| RIOXX Funder/Project Grant: |
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