title: Inflammation as a Therapeutic Target for Diabetic Neuropathies.
abstract: Diabetic neuropathies (DNs) are one of the most prevalent chronic complications of diabetes and a major cause of disability, high mortality, and poor quality of life. Given the complex anatomy of the peripheral nervous system and types of fiber dysfunction, DNs have a wide spectrum of clinical manifestations. The treatment of DNs continues to be challenging, likely due to the complex pathogenesis that involves an array of systemic and cellular imbalances in glucose and lipids metabolism. These lead to the activation of various biochemical pathways, including increased oxidative/nitrosative stress, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage, cyclooxygenase-2 activation, endothelial dysfunction, altered Na(+)/K(+)-ATPase pump function, impaired C-peptide-related signaling pathways, endoplasmic reticulum stress, and low-grade inflammation. This review summarizes current evidence regarding the role of low-grade inflammation as a potential therapeutic target for DNs.
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Metabolism Endocrinology and Diabetes, University of Michigan, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI, 48105, USA. rpbusui@umich.edu.
authors.forename: Rodica
authors.initials: R
authors.lastname: Pop-Busui
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Metabolism Endocrinology and Diabetes, University of Michigan, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI, 48105, USA. ang@med.umich.edu.
authors.forename: Lynn
authors.initials: L
authors.lastname: Ang
authors.affiliation: The Division of Metabolism, Endocrinology and Diabetes, Dominos Farms, Lobby C, Suite 1300 24 Frank Lloyd Wright Drive, PO Box 451, Ann Arbor, MI, 48106-0451, USA. crysholm@med.umich.edu.
authors.forename: Crystal
authors.initials: C
authors.lastname: Holmes
authors.affiliation: Department of Surgery, Section of Vascular Surgery, University of Michigan Health System, 1500 East Medical Center Dr, SPC 5867, Ann Arbor, MI, 48109, USA. kgallag@med.umich.edu.
authors.forename: Katherine
authors.initials: K
authors.lastname: Gallagher
authors.affiliation: Department of Neurology, University of Michigan, 5017 AATBSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA. efeldman@umich.edu.
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003925:Diabetic Angiopathies; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000150:complications; D018384:Oxidative Stress; D011788:Quality of Life; D014945:Wound Healing
keywords: Chronic inflammation; Diabetic neuropathy; Inflammatory cytokines; Peripheral nerve dysfunction