Ordög T, Takayama I, Cheung W K, Ward S M, Sanders K M
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno 89557, USA.
Diabetes. 2000 Oct;49(10):1731-9. doi: 10.2337/diabetes.49.10.1731.
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.
长期患糖尿病的患者通常会出现胃神经肌肉功能障碍（胃病变），症状从餐后腹胀到反复呕吐不等。一般认为自主神经病变是糖尿病性胃病变以及胃排空（胃轻瘫）和容受性舒张潜在损害的原因，但具体机制尚未阐明。最近，人们认识到 Cajal 间质细胞产生电起搏活动并介导胃中的运动神经传递。间质细胞的缺失或缺陷可能导致糖尿病性胃轻瘫的发展。通过测量胃排空以及监测环形平滑肌细胞中的自发和诱发电活动，对自发性糖尿病 NOD/LtJ 小鼠的胃动力进行了表征。通过 Kit 免疫荧光和透射电子显微镜研究了 Cajal 间质细胞。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 间质细胞在胃远端大量减少，并且这些细胞与肠神经末梢之间通常紧密的联系很少见。我们的观察结果表明，Cajal 间质细胞的损伤可能在糖尿病性胃病变的发病机制中起关键作用。
