Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells

Abstract

The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells.

Pharmacological inhibitors of β-cell dysfunction and death as therapeutics for diabetes

“…bcells are susceptible to formation of ROS because of low expression of anti-oxidative enzymes such as catalase, superoxide dismutase and glutathione peroxidase. Increased ROS formation induces bcell damages (for review see [44][45][46][47][48]. As example, excessive production of ROS by the phagocyte-like NADPH oxidase2 (Nox2) drives b-cells toward oxidative damages.…”

“…Chronic exposure of b-cells to high glucose leads to increased ROS formation (for review see [44][45][46][47][48]. The b-oxidation of saturated non-esterified fatty acids in peroxisomes and mitochondria generate hydrogen peroxide.…”

“…The b-oxidation of saturated non-esterified fatty acids in peroxisomes and mitochondria generate hydrogen peroxide. Several antioxidants were reported to protect b-cells against ROS-induced damages (44)(45)(46)(47)(48). As an example, a major flavanone glycoside in citrus species, naringin, was found to decrease ROS accumulation, and to exert protective effects on islet dysfunction and diabetes by amelioration of hyperglycemia (150).…”

The Pancreatic Beta Cell: Editorial

“…This issue focuses on the molecular mechanisms that control beta cell mass expansion and survival, particularly emphasising significant pathways for mature beta cell function. The contributions cover a broad range of topics, including the impact of oxidative stress on beta cells [ 1 , 2 , 3 ], inter-tissular communication [ 4 , 5 , 6 , 7 ], and master regulators of beta cell mass and function [ 8 , 9 , 10 ], among others.…”

“…Mukai and colleagues [ 1 ] reviewed the role of oxidative stress and beta cell antioxidant mechanisms, summarizing how the low expression of antioxidant enzymes in beta cells and oxidative stress can impair insulin secretion. The authors suggested that nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the beta cell antioxidant response.…”