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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Perspectives in Diabetes| September 27 2021
What Regulates Basal Insulin Secretion and Causes Hyperinsulinemia?
Barbara E. Corkey ;
Jude T. Deeney;
Matthew J. Merrins
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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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