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Free Radicals and Islet Function

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Systems Biology of Free Radicals and Antioxidants

Abstract

Pancreatic β-cells secrete insulin in response to changes in extracellular glucose concentration. However, persistent hyperglycemia during diabetes creates a redox imbalance resulting from overproduction of reactive oxygen species (ROS). Although a cell’s intracellular defense mechanism tries to cope with increased ROS levels, excess ROS impairs the integrity and physiological function of biomolecules and therefore affects viability and functionality of cells. This overproduction of ROS along with compromised antioxidant defenses leads to oxidative stress (OS). An organ’s intrinsic defense mechanism protects against this excess generation of ROS and therefore its susceptibility to (OS) is determined by its defense mechanism and ability to repair DNA damage caused by ROS. Islets have poor defense mechanisms and also are not capable of efficiently repairing oxidatively damaged DNA compared to other tissues. This explains the extraordinary sensitivity of islets to OS. In an attempt to strengthen their defense mechanisms, several strategies including oral administration of antioxidants and over-expression of genes responsible for antioxidant enzymes have proven to be successful. However, the reason for this low sensitivity of islets in comparison to other organs remains unresolved.

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Abbreviations

8-OHdG:

8-Hydroxy-2-deoxyguanosine

AOEs:

Antioxidant enzymes

CAT:

Catalase

ETC:

Electron transport chain

GCL:

Glutamate-cysteine ligase

GPx:

Glutathione peroxidase

Grx:

Glutaredoxin

GSH:

Glutathione

GSIS:

Glucose-stimulated insulin secretion

H2O2 :

Hydrogen peroxide

HNE:

4-Hydroxy2-nonenal

JNK:

c-jun NH2-terminal kinase

MCP-1:

Monocyte chemoattractant protein-1

MDA:

Malondialdehyde

NADPH:

Nicotinamide adenine dinucleotide phosphate

NK-κB:

Nuclear factor-κB

NO:

Nitric oxide

NOS:

Nitric oxide synthase

O2 •− :

Superoxide radical

OH•− :

Hydroxyl radical

OS:

Oxidative stress

p38MAPK:

p38 mitogen-activated kinase

PDX1:

Pancreatic and duodenal homeobox 1

Prx:

Peroxiredoxin

PTP:

Protein-tyrosine phosphatase

RNS:

Reactive nitrogen species

ROO• :

Peroxyl radical

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TCA:

Tricarboxylic acid cycle

Trx:

Thioredoxin

UCP:

Uncoupling protein

ZDF rats:

Zucker diabetic fatty rats

ZLF rats:

Zucker lean fatty rats

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Authors and Affiliations

  1. Department of Zoology, University of Pune, Pune, 411007, India

    Jhankar Acharya & Saroj Ghaskadbi

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  1. Jhankar Acharya
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  2. Saroj Ghaskadbi
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Correspondence to Jhankar Acharya .

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  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Acharya, J., Ghaskadbi, S. (2014). Free Radicals and Islet Function. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_154

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