Islets and their antioxidant defense

Abstract

Pancreatic β-cells secrete insulin in response to changes in extracellular glucose concentration. Persistent hyperglycemia during diabetes exerts toxic effects on islets by creating redox imbalance arising from overproduction of reactive oxygen species (ROS). ROS accumulation disturbs the integrity and physiological function of cellular biomolecules impairing viability and functionality of cells. Susceptibility of an organ to oxidative stress (OS) is determined by its defense mechanism and ability to repair DNA damage caused by ROS. Weak defense status of islets along with its inefficiency to repair oxidative DNA damage as compared to other tissues renders it extraordinarily sensitive to OS. Realizing the vulnerability of islet cells to oxidative damage, several efforts to boost their defense mechanism in the form of oral administration of antioxidants and overexpression of genes responsible for antioxidant enzymes have proven successful. Recently accountability for this low antioxidant defense of islets have been given by correlating it with its metabolic evolution.

Deriving at candidate genes of metabolic stress from pancreas of WNIN/GR-Ob mutant rats

“…Inflammation as an intrinsic mechanism to facilitate toward islet dysfunction have been well documented in type 1 diabetes (T1D), 15 obese-T2D 1 as well as in T2D with IR. 16 There have been several confounding factors such as tissue hypertrophy/hyperplasia, 17 oxidative stress 4,10 and apoptosis 17 eventually complementing the chronic inflammatory conditions, 2 in addition to environmental, genetic and epigenetic influences. 18 Mutants demonstrated for an increased expression of TNFα and IL-6, 8 similar to data reported in NOD mice, 19 and which correlated with an increased macrophage infiltration vis-a-vis inflammation.…”

“…These observations were significant due to the fact that these mutants have the natural occurrence of obesity/IR/IGT almost similar to the pre-clinical/clinical scenario, unlike the genetically manipulated or experimental models which have their limitations to extrapolate with human subjects. 9 It is of utmost importance to note that β-cells of pancreas have an inherent weak antioxidant system compared with any other organs in the body 4 and persistent IR, hyperglycemia, or HI predisposes them to a state of profound stress 4,10 and dysregulation of function. 4,10 We hypothesize here that, these mutants would form an ideal model system to study the gravity of metabolic insult/ inflammation using pancreas as the target tissue.…”

“…9 It is of utmost importance to note that β-cells of pancreas have an inherent weak antioxidant system compared with any other organs in the body 4 and persistent IR, hyperglycemia, or HI predisposes them to a state of profound stress 4,10 and dysregulation of function. 4,10 We hypothesize here that, these mutants would form an ideal model system to study the gravity of metabolic insult/ inflammation using pancreas as the target tissue. To prove this, we performed global gene expression (microarray) from pancreas of both mutants (−/−) and parental WNIN controls to assess the magnitude of in situ metabolic lesion.…”

“…[1][2][3] Indeed, obesity/IR/T2D depict a state of low grade inflammation with increase in the generation of reactive oxygen species (ROS), which could have an impact on β-cells functions leading to abnormal glucose handling. 4 There has been a surge in recent times to explore for candidate genes vis-a-vis molecular signatures to mark the disease state with phenotypic features documented with MS.…”

Catalase polymorphism May Influence the Pathogenesis of Diabetes Mellitus

“…The physiological function of bimolecular and their integrity is impaired by ROS accumulation. The susceptibility to this stress, that can impair the cells function and viability, can be determined by their ability to repair the damage to DNA, made by the oxidative stress [38]. The defense mechanism that CAT provides may be affected by its genotype (ie.…”