The roles of streptozotocin neurotoxicity and neutral endopeptidase in murine experimental diabetic neuropathy.
We demonstrated that inhibition of neutral endopeptidase (NEP), a protease that degrades vaso- and neuroactive peptides, improves vascular and neural function in diabetic animal models. In this study we explored the role of NEP in neuropathy related to either insulin-deficient diabetes or diet-induced obesity using NEP deficient (-/-) mice. Initial studies showed that streptozotocin, in the absence of subsequent hyperglycemia, did not induce nerve conduction slowing or paw thermal hypoalgesia. Glucose disposal was impaired in both C57Bl/6 and NEP -/- mice fed a high fat diet. Thermal hypoalgesia and nerve conduction slowing were present in both streptozotocin-diabetic and high fat fed C57Bl/6 mice but not in NEP -/- mice exposed to either streptozotocin-induced diabetes or a high fat diet. These studies suggest that streptozotocin does not induce neurotoxicity in mice and that NEP plays a role in regulating nerve function in insulin-deficient diabetes and diet-induced obesity.
Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA.
Eric
E
Davidson
Lawrence
L
Coppey
Bao
B
Lu
Victor
V
Arballo
Nigel A
NA
Calcutt
Craig
C
Gerard
Mark
M
Yorek
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000209:etiology; D003929:Diabetic Neuropathies / Q000201:enzymology*; D004041:Dietary Fats / Q000008:administration & dosage; D006358:Hot Temperature; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology; D015260:Neprilysin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009422:Nervous System Diseases / Q000139:chemically induced*; D009431:Neural Conduction; D009765:Obesity / Q000209:etiology; D010147:Pain Measurement; D011984:Sensory Receptor Cells / Q000502:physiology; D013311:Streptozocin / Q000633:toxicity*
D004041:Dietary Fats; D013311:Streptozocin; D015260:Neprilysin