Abstract
Although cytotoxic, reactive oxygen species (ROS) also function as important intracellular signaling molecules for cellular responses to a variety of physiological stimuli including glucose sensing and insulin secretion in pancreatic β-cells. The involvement of ROS as signaling intermediates suggests that their magnitude would be inversely correlated with the ROS-scavenging activity and antioxidant status in cells. When cells are chronically exposed to oxidative stressor(s), cellular ROS-scavenging capacity is adaptively upregulated, mainly through activation of the nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) and subsequent transcriptional induction of a suite of antioxidant enzymes, including γ-glutamate cysteine ligase catalytic and modifier subunits, glutathione peroxidases, and peroxiredoxins. The induced antioxidant enzymes, meant to maintain intracellular redox homeostasis and limit oxidative damage, may produce an undesired effect by impeding ROS that function as physiological signaling molecules. Thus, ROS, antioxidants, and the cellular adaptive antioxidant response seem to play counteracting roles in regulating β-cell function and glucose homeostasis: while antioxidants protect β-cells from oxidative damage and related dysfunction, they may also blunt glucose-triggered ROS signaling, resulting in reduced glucose-stimulated insulin secretion. These two premises are likely to be relevant to impairments in pancreatic β-cell function occurring in the late and early stage of type 2 diabetes, respectively. Since high dose of exogenous antioxidants may also impede normal intracellular ROS signaling, we highlight the question whether dietary antioxidant supplements have overlooked adverse effects by interfering with physiological ROS signaling.
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Abbreviations
- ADP:
-
Adenosine diphosphate
- ATP:
-
Adenosine-5′-triphosphate
- Ca2+ :
-
Calcium
- cGMP:
-
Cyclic guanosine monophosphate
- GCLC:
-
γ-glutamate cysteine ligase catalytic subunit
- GCLM:
-
γ-glutamate cysteine ligase modifier subunit
- GPXs:
-
Glutathione peroxidases
- GSIS:
-
Glucose-stimulated insulin secretion
- GSH:
-
Reduced glutathione
- GTP:
-
Guanosine-5′-triphosphate
- H2O2 :
-
Hydrogen peroxide
- KATP :
-
ATP-sensitive potassium channel
- NAC:
-
N-acetyl-cysteine
- NADH:
-
Nicotinamide adenine dinucleotide
- NOX:
-
NADPH oxidase
- Nrf2:
-
Nuclear factor erythroid-derived factor 2-related factor 2
- O2 •− :
-
Superoxide
- PPARγ:
-
Peroxisome proliferator-activated receptor γ
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- T1D:
-
Type 1 diabetes
- T2D:
-
Type 2 diabetes
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This research was supported in part by the NIH grant DK76788 (JP) and ES016005 (JP). The content is solely the responsibility of the authors, and they have no conflicts of interest to disclose.
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Pi, J., Zhang, Q., Andersen, M.E. (2014). Reactive Oxygen Species and Antioxidants in Pancreatic β-Cell Function – Yin and Yang. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_159
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