Deficits in sciatic nerve neuropeptide content coincide with a reduction in target tissue nerve growth factor messenger RNA in streptozotocin-diabetic rats: effects of insulin treatment.
The role of sub-optimal neurotrophic support in the aetiology of the sensory neuron dysfunction associated with diabetic neuropathy was investigated. The status of sciatic nerve neuropeptide content was related to target tissue nerve growth factor messenger RNA levels in streptozotocin-diabetic rats. The levels of substance P and calcitonin gene-related peptide in diabetic sciatic nerve were significantly lowered by approximately 50% and 28%, respectively, compared with aged matched controls and insulin-treated diabetic rats (P < 0.01) for both peptides and both comparisons). Measurements of nerve growth factor messenger RNA levels in sensory neuron target tissues, namely foot-skin and soleus muscle, revealed deficits of approximately 50% in diabetic rats, with insulin treatment reversing the decrease in foot-skin but not in soleus muscle. The results show a possible correlation between deficient neuropeptide gene expression in sensory neurons and reduced nerve growth factor messenger RNA levels in target tissue.
Fernyhough
P
P
Department of Pharmacology, Queen Mary and Westfield College, University of London, U.K.
Diemel
L T
LT
Brewster
W J
WJ
Tomlinson
D R
DR
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D015342:DNA Probes; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009479:Neuropeptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism
D015342:DNA Probes; D007328:Insulin; D009414:Nerve Growth Factors; D009479:Neuropeptides; D012333:RNA, Messenger; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide