Inhibition of p38 MAP kinase corrects biochemical and neurological deficits in experimental diabetic neuropathy.
Diabetes is known to activate MAP kinase p38 in sensory neurons in both rats and patients. In vitro, activation of p38 in sensory neurons by combined glucose and oxidant stress causes cell damage or death. Consequently we tested the hypothesis that inhibition of MAP kinase p38 might prevent neuronal dysfunction in rats with experimental diabetes, such as the classical defect of slowed nerve conduction. Thus, treatment of streptozotocin-diabetic rats with the p38 inhibitor SB239063 for the second half of a 12-week diabetes protocol selectively prevented the nerve conduction deficit in sensory neurons. This implicates activation of MAP kinase p38 as an early step in the signal pathway to dysfunction in experimental diabetic neuropathy.
Agthong
Sithiporn
S
Division of Neuroscience, School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Tomlinson
David R
DR
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009422:Nervous System Diseases / Q000188:drug therapy*; D009431:Neural Conduction / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011743:Pyrimidines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C406525:SB 239063