We hypothesize that basal hyperinsulinemia is synergistically mediated by an interplay between increased oxidative stress and excess lipid in the form of reactive oxygen species (ROS) and long-chain acyl-CoA esters (LC-CoA). In addition, ROS production may increase in response to inflammatory cytokines and certain exogenous environmental toxins that mislead β-cells into perceiving nutrient excess when none exists. Thus, basal hyperinsulinemia is envisioned as an adaptation to sustained real or perceived nutrient excess that only manifests as a disease when the excess demand can no longer be met by an overworked β-cell. In this article we will present a testable hypothetical mechanism to explain the role of lipids and ROS in basal hyperinsulinemia and how they differ from glucose-stimulated insulin secretion (GSIS). The model centers on redox regulation, via ROS, and S-acylation–mediated trafficking via LC-CoA. These pathways are well established in neural systems but not β-cells. During GSIS, these signals rise and fall in an oscillatory pattern, together with the other well-established signals derived from glucose metabolism; however, their precise roles have not been defined. We propose that failure to either increase or decrease ROS or LC-CoA appropriately will disturb β-cell function.
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October 2021
Perspectives in Diabetes|
September 27 2021
What Regulates Basal Insulin Secretion and Causes Hyperinsulinemia?
Barbara E. Corkey
;
1Department of Medicine, Boston University School of Medicine, Boston, MA
Corresponding author: Barbara E Corkey, bcorkey@bu.edu
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Jude T. Deeney;
Jude T. Deeney
1Department of Medicine, Boston University School of Medicine, Boston, MA
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Matthew J. Merrins
Matthew J. Merrins
2Department of Biomolecular Chemistry and Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Wisconsin–Madison School of Medicine and Public Health, Madison, WI
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Corresponding author: Barbara E Corkey, bcorkey@bu.edu
Diabetes 2021;70(10):2174–2182
Article history
Received:
March 15 2021
Accepted:
July 28 2021
Citation
Barbara E. Corkey, Jude T. Deeney, Matthew J. Merrins; What Regulates Basal Insulin Secretion and Causes Hyperinsulinemia?. Diabetes 1 October 2021; 70 (10): 2174–2182. https://doi.org/10.2337/dbi21-0009
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