Depletion of peptidergic innervation in the gastric mucosa of streptozotocin-induced diabetic rats.
Autonomic neuropathy affecting the gastrointestinal system is a major presentation of diabetic neuropathy. Changes in the innervation of gastric mucosa or muscle layers can contribute to gastrointestinal symptoms. The present study investigated this issue by quantitatively analyzing the immunohistochemical patterns of the gastric innervation in rats with streptozotocin (STZ)-induced diabetes. In control rats, calcitonin gene-related peptide (CGRP) and substance P (SP) (+) nerve fibers appeared in the gastric mucosa and muscle layers. Double immunohistochemical staining showed that immunoreactivities for SP and CGRP were co-localized with a pan-neuronal marker protein gene product 9.5. Both SP (+) nerve fibers (p<0.001) and CGRP (+) nerve fibers (p<0.005) were decreased in the gastric mucosa within 4 weeks of diabetes; the reduction persisted throughout 24 weeks. Diabetic rats treated with insulin did not show decrease of SP or CGRP (+) fibers in the mucosa 4 weeks after STZ injection (p>0.05). There was no significant change in SP (+) nerve fibers (p>0.05) or CGRP (+) nerve fibers (p>0.05) of the gastric muscle layers. Reverse transcription-polymerase chain reaction (RT-PCR) showed that the expression levels of SP and CGRP mRNA in the thoracic dorsal root ganglia were similar between diabetic and control animals (p>0.05). Qualitative and quantitative ultrastructural examinations on the gastric mucosa documented unmyelinated nerve degeneration. These results suggest the existence of gastric sensory neuropathy in STZ-induced diabetes, and this pathology provides a foundation for understanding diabetic gastropathy.
Lin
Yen-Yu
YY
Department of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Tseng
To-Jung
TJ
Hsieh
Yu-Lin
YL
Luo
Kai-Ren
KR
Lin
Whei-Min
WM
Chiang
Hao
H
Hsieh
Sung-Tsang
ST
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D005753:Gastric Mucosa / Q000294:innervation* / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*
D010455:Peptides; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide