Update on the pathogenesis of diabetic neuropathy.
Peripheral diabetic neuropathy (PDN) affects up to 60% to 70% of diabetic patients, and is the leading cause of foot amputation. The pathogenesis of PDN involves multiple mechanisms. The findings obtained in 1999 to 2003 support the role of previously established mechanisms such as increased aldose reductase activity, nonenzymatic glycation or glyco-oxidation, activation of protein kinase C, enhanced oxidative stress, impaired neurotrophic support, and reveal the importance of new downstream effectors of oxidative injury. Those include mitogen-activated protein kinases and poly (ADP-ribose) polymerase that are activated by diabetes, and contribute to such neuropathic changes as motor and sensory nerve conduction deficits, decreased nerve blood flow, and energy failure. Further studies are needed to understand the role of other signaling pathways as well as interactions among previously discovered mechanisms in the pathogenesis of PDN.
Obrosova
Irina G
IG
University of Michigan, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, 1150 West Medical Center Drive, MSRB II, Room 5570, Ann Arbor, MI 48109-0678, USA. iobrosso@umich.edu
D003925:Diabetic Angiopathies / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004789:Enzyme Activation; D006031:Glycosylation; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000502:physiology; D009420:Nervous System / Q000098:blood supply; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D009414:Nerve Growth Factors; D011065:Poly(ADP-ribose) Polymerases