Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.

Abstract

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.

Prevalence of Delayed Gastric Emptying in Diabetic Patients and Relationship to Dyspeptic Symptoms

“…Also, it cannot be excluded that the number of subjects studied was too small to detect a relationship between poor glycemic control and delayed gastric emptying. The delay in gastric emptying observed in our studies is most likely due to reversible or irreversible autonomic dysfunction at the level of the extrinsic nervous system and/or the myenteric plexus (25)(26)(27). Without doubt, the actual blood glucose concentration plays an important role in reversible autonomic dysfunction because it has been shown that blood glucose concentration affects vagal tone and blunt gastrocolonic reflexes (28,29).…”

Analysis of multiple factors of postsurgical gastroparesis syndrome after pancreaticoduodenectomy and cryotherapy for pancreatic cancer

“…Gastric dysrhythmias (tachygastrias and bradygastrias) are disturbances of the normal gastric pacesetter potentials and are associated with such symptoms as nausea, epigastric fullness, bloating and delayed gastric emptying. Ordog et al [14] suggest that damage to interstitial cells of Cajal may play a key role in the pathogenesis of diabetic gastropathy. Meanwhile, Zarate et al [15] reported that histological and immunohistochemical study of the resected specimen showed hypoganglionosis, neuronal dysplasia, and marked reduction in both myenteric and intramuscular interstitial cells of Cajal in patients with idiopathic gastroparesis.…”

Epigenetics of gastrointestinal diseases: notes from a workshop

“…Tamas Ordog described progress in understanding the epigenetic regulation of the interstitial cells of Cajal (ICC), which are electrical pacemaker and neuromodulator cells of the GI neuromuscular system. Alterations in ICC number or function contribute to dysregulation of gastric emptying in diabetes [11–13]. ICC differentiation and function depend on expression of the receptor tyrosine kinase, Kit.…”