Insulin-like growth factor I reverses experimental diabetic autonomic neuropathy.
Recent studies have suggested a role for neurotrophic substances in the pathogenesis and treatment of diabetic neuropathy. In this study, the effect of insulin-like growth factor I (IGF-I) on diabetic sympathetic autonomic neuropathy was examined in an experimental streptozotocin-induced diabetic rat model. Two months of IGF-I treatment of chronically diabetic rats with established neuroaxonal dystrophy (the neuropathological hallmark of the disease) involving the superior mesenteric ganglion and ileal mesenteric nerves resulted in nearly complete normalization of the frequency of neuroaxonal dystrophy in both sites without altering the severity of diabetes. Treatment with low-dose insulin (to control for the transient glucose-lowering effects of IGF-I) failed to affect the frequency of ganglionic or mesenteric nerve neuroaxonal dystrophy or the severity of diabetes. The striking improvement in the severity of diabetic autonomic neuropathy shown with IGF-I treatment in these studies and the fidelity of the rat model to findings in diabetic human sympathetic ganglia provide promise for the development of new clinical therapeutic strategies.
Schmidt
R E
RE
Division of Neuropathology, Department of Pathology, Washington University School of Medicine, St. Louis, Missouri, USA. reschmidt@pathology.wustl.edu
Dorsey
D A
DA
Beaudet
L N
LN
Plurad
S B
SB
Parvin
C A
CA
Miller
M S
MS
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure
D013311:Streptozocin; D007334:Insulin-Like Growth Factor I