Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

Abstract

Diabetic polyneuropathy (DPN) is defined as peripheral nerve dysfunction. There are three main alterations involved in the pathologic changes of DPN: inflammation, oxidative stress, and mitochondrial dysfunction. Inflammation induces activation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases. Oxidative stress induced by hyperglycemia is mediated by several identified pathways: polyol, hexosamine, protein kinase C, advanced glycosylation end-products, and glycolysis. In addition, mitochondrial dysfunction accounts for most of the production of reactive oxygen and nitrosative species. These free radicals cause lipid peroxidation, protein modification, and nucleic acid damage, to finally induce axonal degeneration and segmental demyelination. The prevalence of DPN ranges from 2.4% to 78.8% worldwide, depending on the diagnostic method and the population assessed (hospital-based or outpatients). Risk factors include age, male gender, duration of diabetes, uncontrolled glycaemia, height, overweight and obesity, and insulin treatment. Several diagnostic methods have been developed, and composite scores combined with nerve conduction studies are the most reliable to identify early DPN. Treatment should be directed to improve etiologic factors besides reducing symptoms; several approaches have been evaluated to reduce neuropathic impairments and improve nerve conduction, such as oral antidiabetics, statins, and antioxidants (alpha-lipoic acid, ubiquinone, and flavonoids).

The metabolic syndrome alters the miRNA signature of porcine adipose tissue‐derived mesenchymal stem cells

“…The AP1 family members Fra1 and Fra2 modulates cell proliferation, differentiation and oxidative stress in Diabetes Mellitus [26]. Specifically, miR-7, enriched in MetS-EVs, may lead to inhibition of Specificity protein-1 (SP1), a gene associated with the AP1 family members Fra1 and Fra2 pathway, resulting ROS-induced tissue injury [27].…”

Dynamic Properties of Skeletal Muscle Contraction in Rats with Diabetes

“…Independent causes of the risk of this serious complication of diabetes mellitus are age, male gender, unsatisfactory control of the level of glycaemia, elevated lipid levels in the blood, height, overweight and obesity, and insulin treatment [12][13][14][15][16]. Thus, the pathogenesis of diabetic polyneuropathy is multifactorial.…”

Hepatic fatty acid biosynthesis in KK‐Ay mice is modulated by administration of persimmon peel extract: A DNA microarray study

“…We assumed that the reduction in reactive oxygen species (ROS) caused by the administration of PP extract containing antioxidants (carotenoids, polyphenols, vitamin E, etc.) would suppress inflammation caused by the overproduction of ROS in diabetes mellitus (Roman‐Pintos, Villegas‐Rivera, Rodriguez‐Carrizalez, Miranda‐Diaz, & Cardona‐Munoz, ). Furthermore, downregulation of genes involved in the “cellular response to stress” ( Cdkn1 , Btg2 , Kif22 , Brca1 , Hspa1 , Cry1 , Kif22 , Errfl1 , Scara5 ) is likely due to the reduction of stressors, such as ROS, by PP extract.…”