A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus.
BACKGROUND
Gastrointestinal motility is impaired in patients with diabetes mellitus (DM). Interstitial cells of Cajal (ICC) in the gastrointestinal tract play a central role in gastrointestinal motility. The present study examined whether ICC density, or expression of neuronal nitric oxide synthase (nNOS)- and substance P (SP)-containing nerves in the gastric antrum, were altered in patients with type 2 DM.


METHODS
Paraffin-embedded gastric specimens from 51 controls and 36 male DM patients with gastric cancer were used for immunohistochemistry. Serial sections were stained with Kit and mast cell tryptase-specific antibodies. Fresh-frozen gastric specimens from patients with gastric cancer were used for immunofluorescence. The specimens were stained with antibodies to Kit, nNOS, and SP, and levels of expression of these three markers were compared between controls and DM patients.


RESULTS
ICC density in the inner circular muscle layer, but not in the myenteric plexus, was lower in patients with severe DM than in controls in paraffin-embedded specimens. In addition, decreased expression of nNOS and SP accompanied by reduced ICC density was observed in frozen specimens from patients with DM.


CONCLUSIONS
These results suggest that lower gastric ICC, nNOS, and SP densities in patients with DM may be associated with the pathogenesis of diabetic gastroparesis.
Iwasaki
Hirohiko
H
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Kajimura
Masayoshi
M
Osawa
Satoshi
S
Kanaoka
Shigeru
S
Furuta
Takahisa
T
Ikuma
Mutsuhiro
M
Hishida
Akira
A
D015415:Biomarkers; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D005753:Gastric Mucosa / Q000294:innervation* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009197:Myenteric Plexus / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D012189:Retrospective Studies; D013373:Substance P / Q000096:biosynthesis*
D015415:Biomarkers; D013373:Substance P; D052248:Nitric Oxide Synthase Type I