Loss of interstitial cells of cajal and inhibitory innervation in insulin-dependent diabetes.
OBJECTIVE
Gastrointestinal complications of long-standing diabetes include nausea, vomiting, abdominal pain, diarrhea, and constipation. The pathophysiology underlying these symptoms is poorly understood. Recent evidence suggests an important role for interstitial cells of Cajal in controlling gastrointestinal motility. The aim of this study was to determine changes in interstitial cells of Cajal and enteric innervation in a patient with insulin-dependent diabetes.


METHODS
A full thickness jejunal biopsy was obtained from a 38-year-old insulin-dependent diabetic with evidence for diabetic gastroenteropathy. Immunohistochemistry, confocal microscopy, and 3-dimensional reconstruction techniques were used to quantify changes in the volume of interstitial cells of Cajal and enteric innervation.


RESULTS
Interstitial cells of Cajal were markedly decreased throughout the entire thickness of the jejunum. A decrease in neuronal nitric oxide synthase, vasoactive intestinal peptide, PACAP, and tyrosine hydroxylase immunopositive nerve fibers was observed in circular muscle layer while substance P immunoreactivity was increased.


CONCLUSIONS
The data suggest that long-standing diabetes is associated with a decrease in interstitial cells of Cajal volume and a decrease in inhibitory innervation, associated with an increase in excitatory innervation. The changes in interstitial cells of Cajal volume and enteric nerves may underlie the pathophysiology of gastrointestinal complications associated with diabetes and suggest future therapeutic targets.
He
C L
CL
Department of Physiology and Biophysics, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street NW, Rochester, MN 55905, USA.
Soffer
E E
EE
Ferris
C D
CD
Walsh
R M
RM
Szurszewski
J H
JH
Farrugia
G
G
D000328:Adult; D015415:Biomarkers; D001706:Biopsy; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology*; D017615:Enteric Nervous System / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007583:Jejunum / Q000294:innervation; D009433:Neural Inhibition / Q000502:physiology*; D013869:Thiolester Hydrolases / Q000032:analysis; D043222:Ubiquitin Thiolesterase
D015415:Biomarkers; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase