The Role of Oxidative Stress, Mitochondrial Function, and Autophagy in Diabetic Polyneuropathy

Abstract

Diabetic polyneuropathy (DPN) is the most frequent and prevalent chronic complication of diabetes mellitus (DM). The state of persistent hyperglycemia leads to an increase in the production of cytosolic and mitochondrial reactive oxygen species (ROS) and favors deregulation of the antioxidant defenses that are capable of activating diverse metabolic pathways which trigger the presence of nitro-oxidative stress (NOS) and endoplasmic reticulum stress. Hyperglycemia provokes the appearance of micro- and macrovascular complications and favors oxidative damage to the macromolecules (lipids, carbohydrates, and proteins) with an increase in products that damage the DNA. Hyperglycemia produces mitochondrial dysfunction with deregulation between mitochondrial fission/fusion and regulatory factors. Mitochondrial fission appears early in diabetic neuropathy with the ability to facilitate mitochondrial fragmentation. Autophagy is a catabolic process induced by oxidative stress that involves the formation of vesicles by the lysosomes. Autophagy protects cells from diverse stress factors and routine deterioration. Clarification of the mechanisms involved in the appearance of complications in DM will facilitate the selection of specific therapeutic options based on the mechanisms involved in the metabolic pathways affected. Nowadays, the antioxidant agents consumed exogenously form an adjuvant therapeutic alternative in chronic degenerative metabolic diseases, such as DM.

Pulmonary vascular dysfunction in metabolic syndrome

“…; Fowler, ), eyes (Grammas & Riden, ; Frank, ), brain (Sifuentes‐Franco et al . ), and heart (Yuan et al . , ).…”

“…; Sifuentes‐Franco et al . ); however, there is less information available regarding the effects of metabolic syndrome on pulmonary vascular function (Pugh & Hemnes, ). In this review, we will discuss the alteration of pulmonary vascular functions in diabetes, insulin resistance, obesity and dyslipidaemia.…”

Longitudinal Intravital Imaging of Biosensor-labeled In Situ Islet Beta Cells

“…Here, we used roGFP2 containing human glutaredoxin-1 (Grx1-roGFP2), which is sensitive to the glutathione redox cycle in the cytoplasm 6 . Though ROS is primarily generated in the mitochondria, literature supports the idea that the unregulated release of mitochondrial ROS into the cytosol and enhanced cytoplasmic production of ROS are key features in the progression of cellular oxidative stress 7,8 . We first generated an adenovirus containing Grx1-roGFP2 under the control of a hybrid insulin/rabbit beta globin promoter 9 (Ad-lNS-Grx1-roGFP2) to label and selectively measure ROS dynamics in islet β-cells.…”

Photobiomodulation induces antinociception, recovers structural aspects and regulates mitochondrial homeostasis in peripheral nerve of diabetic mice

“…In addition to the decrease on axoplasma‐myelin separation and increased C fibers count, herein it was demonstrated, for the first time, that PBM increases the total number of mitochondria in diabetic mice and improves their metabolic state demonstrated by the decrease in Parkin levels. Once Parkin is involved in mitophagy, the process by which damaged mitochondria undergo autophagy , it is plausible to speculate that PBM regulates mitochondrial metabolism inducing a direct protecting or repairing effect on diabetic‐treated mice.…”