title: Diabetic Neuropathy: Update on Pathophysiological Mechanism and the Possible Involvement of Glutamate Pathways.
abstract: BACKGROUND
  Diabetic neuropathy is a common complication of diabetes. It adversely affects the lives of most diabetics. It is the leading cause of non-traumatic limb amputation. Diabetic autonomic neuropathy can target any system and increases morbidity and mortality. Treatment begins with adequate glycemic control but despite this, many patients go on to develop neuropathy which suggests there are additional and unidentified, as yet, pathological mechanisms in place. Although several theories exist, the exact mechanisms are not yet established. Disease modifying treatment requires a more complete understanding of the mechanisms of disease. Pathways Involved: This review discusses the potential pathological mechanisms of diabetic neuropathy, including the polyol pathway, hexosamine pathway, protein kinase C, advanced glycation end product formation, polyADP ribose polymerase, and the role of oxidative stress, inflammation, growth factors and lipid abnormalities. Finally it focuses on how possible changes in glutamate signaling pathways fit into the current theories.
  
  
  CONCLUSIONS
  Insights into the mechanisms involving gene expression in diabetic neuropathy can help pinpoint genes with altered expression. This will help in the development of novel alternative therapeutic strategies to significantly slow the progression of neuropathy in susceptible individuals and perhaps even prevention.
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain. United Arab Emirates.
authors.forename: Nadia
authors.initials: N
authors.lastname: Hussain
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain. United Arab Emirates.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Adrian
mesh_terms: D000818:Animals; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011108:Polymers / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D006595:Hexosamines; D011108:Polymers; C024617:polyol; D018698:Glutamic Acid; D011493:Protein Kinase C
keywords: Diabetic neuropathy; autonomic neuropathy; glutamate; pathophysiology