Early neurochemical changes in the autonomic neuropathy of the gut in experimental diabetes.
Some neurochemical changes in the gut of rats after five weeks of alloxan-induced diabetes were investigated. It was found that at this stage of diabetes the changes were restricted mainly to the small intestine with a special selectivity for the duodenum. No changes were found in the most part of the large intestine and rectum. The methionine-enkephalin content was markedly reduced throughout the small intestine, while vasoactive intestinal polypeptide was increased in duodenum, ileum and caecum. Substance P content was unaffected, while at later stages of the disease it was significantly reduced in the entire small intestine. Sympathetic noradrenaline and intrinsic serotonin contents were significantly increased in the duodenum and unchanged throughout the rest of the intestine. These data suggest that the small intestine and caecum might be the early target of diabetic autonomic neuropathy, that might involve progressively the rest of the large intestine at later stages as recent results have suggested. It is likely that the gastrointestinal dysfunctions, often present in diabetic patients, might also be due to the combined pre-synaptic alterations, and to the functional imbalance between Gs and Gi/Go transduction proteins recently reported. Insulin therapy, begun seven days after alloxan treatment, reduced drastically the hyperglycaemia, restored normal body growth and prevented all the gut neurochemical changes associated with alloxan-induced diabetes.
Gorio
A
A
Department of Pharmacology, Chemotherapy and Medical Toxicology, Faculty of Medicine, University of Milan, Italy.
Di Giulio
A M
AM
Donadoni
L
L
Tenconi
B
B
Germani
E
E
Bertelli
A
A
Mantegazza
P
P
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000294:innervation; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction; D013373:Substance P / Q000032:analysis / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000378:metabolism
D009479:Neuropeptides; D012701:Serotonin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D019204:GTP-Binding Proteins