Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis
Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis
复制标题
DOI：
10.2337/diabetes.49.10.1731
复制
发表时间：
2000-10-01
期刊：
影响因子：
7.7
通讯作者：
Sanders, KM
中科院分区：
文献类型：
--
作者：
Ördög, T;Takayama, I;Sanders, KM
长期糖尿病患者通常患有胃神经肌肉功能障碍（胃病），引起从餐后腹胀到反复呕吐的症状。自主神经病变通常被认为是糖尿病性胃病以及胃排空（胃轻瘫）和接受性舒张的潜在损害的原因，但具体机制尚未阐明。最近，人们已经认识到，Cajal间质细胞产生电起搏活动，并介导胃运动神经传递。间质细胞的缺失或缺陷可能导致糖尿病胃轻瘫的发生。通过测量胃排空和监测环形平滑肌细胞的自发和诱导电活动来表征自发性糖尿病NOD/LtJ小鼠的胃运动。糖尿病小鼠出现胃排空延迟、电起搏受损和运动神经传递减少。Cajal间质细胞在远端胃中大大减少，这些细胞和肠神经末梢之间的正常密切联系是罕见的。提示Cajal间质细胞的损伤在糖尿病性胃病的发病机制中起重要作用。
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.