Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.
Patients with long-standing diabetes commonly suffer from gastric neuromuscular dysfunction (gastropathy) causing symptoms ranging from postprandial bloating to recurrent vomiting. Autonomic neuropathy is generally believed to be responsible for diabetic gastropathy and the underlying impairments in gastric emptying (gastroparesis) and receptive relaxation, but the specific mechanisms have not been elucidated. Recently, it has been recognized that interstitial cells of Cajal generate electrical pacemaker activity and mediate motor neurotransmission in the stomach. Loss or defects in interstitial cells could contribute to the development of diabetic gastroparesis. Gastric motility was characterized in spontaneously diabetic NOD/LtJ mice by measuring gastric emptying and by monitoring spontaneous and induced electrical activity in circular smooth muscle cells. Interstitial cells of Cajal were studied by Kit immunofluorescence and transmission electron microscopy. Diabetic mice developed delayed gastric emptying, impaired electrical pacemaking, and reduced motor neurotransmission. Interstitial cells of Cajal were greatly reduced in the distal stomach, and the normally close associations between these cells and enteric nerve terminals were infrequent. Our observations suggest that damage to interstitial cells of Cajal may play a key role in the pathogenesis of diabetic gastropathy.
Ordög
T
T
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno 89557, USA.
Takayama
I
I
Cheung
W K
WK
Ward
S M
SM
Sanders
K M
KM
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000150:complications; D004195:Disease Models, Animal; D004594:Electrophysiology; D005260:Female; D005455:Fluorescent Antibody Technique; D005746:Gastric Emptying; D005769:Gastrointestinal Motility; D018589:Gastroparesis / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000503:physiopathology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D013270:Stomach / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission
D019009:Proto-Oncogene Proteins c-kit