Redox imbalance stress in diabetes mellitus: Role of the polyol pathway

Abstract

In diabetes mellitus, the polyol pathway is highly active and consumes approximately 30% glucose in the body. This pathway contains 2 reactions catalyzed by aldose reductase (AR) and sorbitol dehydrogenase, respectively. AR reduces glucose to sorbitol at the expense of NADPH, while sorbitol dehydrogenase converts sorbitol to fructose at the expense of NAD+, leading to NADH production. Consumption of NADPH, accumulation of sorbitol, and generation of fructose and NADH have all been implicated in the pathogenesis of diabetes and its complications. In this review, the roles of this pathway in NADH/NAD+ redox imbalance stress and oxidative stress in diabetes are highlighted. A potential intervention using nicotinamide riboside to restore redox balance as an approach to fighting diabetes is also discussed.

Glucolipotoxicity: A Proposed Etiology for Wooden Breast and Related Myopathies in Commercial Broiler Chickens

“…Excess glucose is also consumed in the polyol pathway, a two-step process that converts glucose first to sorbitol and then to fructose (Yan, 2018). Upregulation of the polyol pathway, specifically its first step, in wooden breast and white striping is supported by an accumulation of sorbitol in the pectoralis major (Abasht et al, 2016;Boerboom et al, 2018).…”

“…Most ROS are generated as normal by-products during mitochondrial electron transport, specifically at respiratory complexes I and III of the oxidative phosphorylation pathway (Rousset et al, 2004), and are prevented from reaching damaging levels by various cellular defenses such as superoxide dismutase and glutathione peroxidase (Anderson and Neufer, 2006). Potential genetic variation in antioxidant response may be a key contributor to wooden breast susceptibility in broilers, as altered redox homeostasis can inhibit the activity of anti-oxidant enzymes and increase ROS production at mitochondrial respiratory complex I (Yabe-Nishimura, 1998; Chung, 2004;Yan, 2018). In diabetes, the polyol pathway is believed to play a critical role in oxidative stress and vascular damage due to its derangement of redox homeostasis (Yabe-Nishimura, 1998;Chung, 2004;Yan, 2018).…”

“…Potential genetic variation in antioxidant response may be a key contributor to wooden breast susceptibility in broilers, as altered redox homeostasis can inhibit the activity of anti-oxidant enzymes and increase ROS production at mitochondrial respiratory complex I (Yabe-Nishimura, 1998; Chung, 2004;Yan, 2018). In diabetes, the polyol pathway is believed to play a critical role in oxidative stress and vascular damage due to its derangement of redox homeostasis (Yabe-Nishimura, 1998;Chung, 2004;Yan, 2018). The first of two reactions in the pathway is conversion of glucose and NADPH to sorbitol and NADP+ by aldose reductase and is suggested to be upregulated in the pectoralis major of affected birds based on the accumulation of sorbitol (Abasht et al, 2016;Boerboom et al, 2018).…”

Intestinal Fructose and Glucose Metabolism in Health and Disease

“…Further research demonstrated the presence of an active polyol pathway in tissues other than those involved in metabolizing dietary fructose, such as the human brain [98][99][100]. Numerous studies using animal models have linked the polyol pathway to metabolic alterations such as obesity, insulin resistance, diabetes, diabetic nephropathy, chronic kidney disease, acute kidney injury, blood pressure, and MetS [101][102][103][104]. Nonetheless, although the presence of an active polyol pathway has been described in humans, and mounting evidences obtained in animal models of the importance of this pathway in diseases, its significance in human metabolic diseases awaits further confirmation.…”

Цукровий Діабет І Мозковий Інсульт: Сучасний Погляд На Проблему

“…Гіперглікемія також призводить до посиленої активації поліолового шляху окиснення глюкози зі зростанням швидкості продукції сорбітолу й фруктози. Останні погано проникають через плазмолему й накопичуються в клітинах, підвищуючи осмолярність, що спричиняє розвиток дегенерації клітин через «гіперосмолярні «вибухи» [15]. Крім того, накопичення сорбітолу в нейронах пригнічує синтез найважливішого компоненту мієліну -міоінозитолу, що є субстратом для синтезу мембранного фосфатидилінозитолу (ендогенного регулювальника мікросомальної Na + K + АТФази), а також для численних різноманітних сигнальних молекулкіназ, які можуть приєднати до інозитолу фосфатну групу.…”