Loss of intramuscular and submuscular interstitial cells of Cajal and associated enteric nerves is related to decreased gastric emptying in streptozotocin-induced diabetes.
Interstitial cells of Cajal (ICC) are associated with afferent innervation and peristalsis of the stomach suggestive of a key role in the pathophysiology of gastroparesis. We studied changes in the density and ultrastructure of ICC and enteric nerves in the streptozotocin-induced diabetes mellitus (STZ-DM) in Wistar rats using immunohistochemistry and electron microscopy. Gastric emptying was studied in vivo by single-photon emission computed tomography. In the STZ-DM antrum, a marked reduction was observed in the density of the intramuscular ICC (ICC-IM) and ICC located at the submucosal border of the circular muscle layer of the antrum (ICC-SM). The surviving ICC showed lamellar bodies and partial vacuolation of the cytoplasm content, loss of connections between ICC-IM and nerves; it appeared that injured ICC-IM developed into fibroblast-like ICC. ICC associated with Auerbach's plexus (ICC-AP) in the antrum and ICC in the fundus were not affected significantly except for a loss of connections with nerve structures. Marked reduction in nerve tissue (Protein Gene Product-9.5 positivity) was also restricted to the muscle layers including nitrergic nerves (neuronal nitric oxide synthase positivity). In vivo assessed gastric emptying was markedly reduced in STZ-DM rats. Our data demonstrate in the STZ-DM rat stomach a decreased density of ICC limited to the antrum and to ICC-IM and ICC-SM, and structural degeneration in ICC-IM and associated nerves with a special emphasis on loss of synaptic connections, accompanied by a decrease in gastric emptying. Hence, in this model of gastroparetic diabetes, regional injury to subsets of ICC and nerves are associated with gastric motor dysfunction.
Wang
X-Y
XY
Department of Medicine, McMaster University, Farncombe Family Digestive Health Research Institute, ON, Canada.
Huizinga
J D
JD
Diamond
J
J
Liu
L W C
LW
D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D017615:Enteric Nervous System / Q000473:pathology*; D005260:Female; D005746:Gastric Emptying / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000000981:diagnostic imaging / Q000294:innervation*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D001786:Blood Glucose