Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose.
Diabetic autonomic neuropathy is a major cause of morbidity and mortality. However, its etiology and treatment remain obscure. Using the in vitro rat superior cervical ganglion model of diabetic neuropathy, we studied the neuroprotective effects of IGF-I on neurite growth and neuronal apoptosis in a high-glucose milieu. In the presence of elevated levels of glucose similar to those seen in poorly controlled diabetics (20 mM above control), there is inhibition of neurite growth, reduction in neurite caliber, beading of neurites, and retraction of the neurite growth cone. High glucose also induces apoptosis in ganglion neurons. In contrast, IGF-I prevented both glucose induced apoptosis and changes in neurites, even after 96 hours. The IGF-I receptor was uniformly distributed throughout the developing neurite and growth cone in control and IGF-I treated neurons, but not with high glucose alone. These findings suggest that high glucose inhibits neurite growth and initiates apoptosis in cultured sympathetic primary neurons, and IGF-I ameliorates these changes. Collectively, these observations suggest that many of the features of diabetic autonomic neuropathy can be reproduced in a tissue culture model using defined conditions, and may have important implications in defining the etiology and treatment of diabetic neuropathy.
Russell
J W
JW
Department of Neurology, University of Michigan, USA. jruss@umich.edu
Feldman
E L
EL
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology; D005947:Glucose / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology*
D007334:Insulin-Like Growth Factor I; D005947:Glucose