Iron Ascorbic Acid-Mediated Oxidative Stress Leads to Abnormal Insulin Secretion in Pancreatic Beta Cells

Authors:

Ntimbane T¹, Spahis S^1,2, Rabasa-Lhoret R^2,3, Mailhot G^1,2 , Berthiaume Y^3,4 and Levy E^1,2*

Special Issue 1

Abstract

Background: Oxidative stress (OxS) is involved in organ damage during the pathogenesis of diabetes, but the relationship between OxS and the deterioration of β-cell function remains unclear. Due to their low expression of many antioxidant enzymes, β-cells may be susceptible to OxS in response to the increased production of reactive oxygen species (ROS) associated with the hyperglycemic condition.

Objectives: In the current study, we investigated the relationship between chemical-induced ROS generation and glucose-stimulated insulin secretion under OxS conditions.

Methods: Murine pancreatic βTC-tet cells were treated with the pro-oxidant iron-ascorbate (0.2 mM/2 mM) complex in the presence or absence of the powerful antioxidant Trolox (1mM).

Results: Chronic exposure of the pancreatic β-cell to the pro-oxidant system iron/ascorbate markedly lowered endogenous antioxidant enzyme defence (catalase and superoxide dismutase) while increasing ROS and lipid peroxidation as noted by measurement of the fluorescent probe CM-H2DCFDA, malondialdehyde and 4-hydroxy-2-nonenal-protein adducts. Concomitantly, glucose-induced insulin secretion was altered and potential mechanisms for insulin output blunting include activation of the inflammatory transcription factor NF-κB, depressed ATP/ADP ratio and reduced arachidonic acid levels. The antioxidant and scavenger compound Trolox prevented the harmful effect of OxS and restored the insulin secretion profile.

Conclusions: Taken together, these findings indicate that OxS may disturb insulin secretion via alterations of various intracellular pathways, a phenomenon that may be prevented by antioxidants.

Keywords:

Oxidative Stress; Pancreatic Cells; Insulin Secretion; Diabetes

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