Reversal of nerve damage in streptozotocin-diabetic rats by acute application of insulin in vitro.
1. Immunohistochemical, immunoblotting and release experiments were performed on ileum from control rats, from 8-week streptozotocin-diabetic rats and from diabetic rats after acute application of insulin in vitro. 2. There was an increase in vasoactive-intestinal-polypeptide-like and a decrease in calcitonin-gene-related-peptide-like immunoreactivity in the myenteric plexus of the diabetic rat ileum, although electrically evoked release of both peptides from enteric nerves was defective. Acute application of insulin in vitro reversed the defective release and changes in immunoreactivity of vasoactive intestinal polypeptide and calcitonin-gene-related peptide seen in the enteric nerves of streptozotocin-diabetic rat ileum. 3. In addition, using a monoclonal neurofilament antibody RT 97 that recognizes a phosphorylated neurofilament epitope present in normal enteric nerves, it was shown that this phosphorylated neurofilament epitope was absent in diabetic nerves, even though a polyclonal neurofilament antibody revealed that neurofilaments were present in both axons and cell bodies of the myenteric plexus of diabetic rat ileum. After only 2 h of insulin incubation in vitro, the phosphorylated neurofilament epitope was again present in the nerves. 4. It is suggested that the abnormal distribution of phosphorylated neurofilaments and defective storage and release of vasoactive intestinal polypeptide and calcitonin-gene-related peptide in the present study may be a more general feature of diabetes. The restoration of these abnormalities by continuous acute insulin application in vitro shown here suggests that the availability of a steady level of insulin might prevent some of the changes which occur in early stages of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
Burnstock
G
G
Department of Anatomy and Developmental Biology, University College London.
Mirsky
R
R
Belai
A
A
D000818:Animals; D002116:Calcitonin / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000628:therapy*; D007082:Ileum / Q000294:innervation* / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use*; D007382:Intermediate Filaments / Q000187:drug effects; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D007328:Insulin; D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide