Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in diabetic db/db mice.
OBJECTIVE
Diabetes mellitus (DM) often causes gastrointestinal dysmotility. Interstitial cells of Cajal (ICC), which express c-kit receptor tyrosine kinase (KIT), are considered the pacemaker cells for gastrointestinal movement. The present study was designed to determine the role of ICC in the pathogenesis of gastroenteropathy in type 2 DM.


METHODS
We examined C57BL/KsJ-db/db mice as a model for type 2 DM. Gastrointestinal motility was evaluated by measuring gastric emptying, whole gut transit time, and isometric tension of the isolated small intestine. The area of KIT-positive cells in the gastrointestinal tract was examined by image analysis of fluorescent immunohistochemistry. The mRNA expression of KIT ligand, stem cell factor (SCF), in the gastrointestinal tract was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Compared with 12-week-old db/+m control mice, diabetic db/db mice of the same age exhibited delayed gastric emptying, prolonged whole gut transit time, irregular frequency of isometric tension in the small intestine, smaller areas of KIT-positive cells in the antrum, small intestine, and colon, and lower mRNA expression levels of SCF in the small intestine and colon.


CONCLUSIONS
We demonstrated disturbed gastrointestinal motility in db/db mice with reduced areas of ICC and expression of SCF. Our results suggest the involvement of ICC in the gastroenteropathy of type 2 DM.
Yamamoto
Takahiro
T
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Watabe
Kenji
K
Nakahara
Masanori
M
Ogiyama
Hideharu
H
Kiyohara
Tatsuya
T
Tsutsui
Shusaku
S
Tamura
Shinji
S
Shinomura
Yasuhisa
Y
Hayashi
Norio
N
D000818:Animals; D048909:Diabetes Complications / Q000209:etiology* / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology*; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000473:pathology*; D005769:Gastrointestinal Motility; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000473:pathology*