Gorio A, Di Giulio A M, Donadoni L, Tenconi B, Germani E, Bertelli A, Mantegazza P
Department of Pharmacology, Chemotherapy and Medical Toxicology, Faculty of Medicine, University of Milan, Italy.
Int J Clin Pharmacol Res. 1992;12(5-6):217-24.
Some neurochemical changes in the gut of rats after five weeks of alloxan-induced diabetes were investigated. It was found that at this stage of diabetes the changes were restricted mainly to the small intestine with a special selectivity for the duodenum. No changes were found in the most part of the large intestine and rectum. The methionine-enkephalin content was markedly reduced throughout the small intestine, while vasoactive intestinal polypeptide was increased in duodenum, ileum and caecum. Substance P content was unaffected, while at later stages of the disease it was significantly reduced in the entire small intestine. Sympathetic noradrenaline and intrinsic serotonin contents were significantly increased in the duodenum and unchanged throughout the rest of the intestine. These data suggest that the small intestine and caecum might be the early target of diabetic autonomic neuropathy, that might involve progressively the rest of the large intestine at later stages as recent results have suggested. It is likely that the gastrointestinal dysfunctions, often present in diabetic patients, might also be due to the combined pre-synaptic alterations, and to the functional imbalance between Gs and Gi/Go transduction proteins recently reported. Insulin therapy, begun seven days after alloxan treatment, reduced drastically the hyperglycaemia, restored normal body growth and prevented all the gut neurochemical changes associated with alloxan-induced diabetes.
研究了四氧嘧啶诱导的糖尿病大鼠五周后肠道中的一些神经化学变化。发现在糖尿病的这个阶段，变化主要局限于小肠，对十二指肠具有特殊的选择性。在大肠和直肠的大部分未发现变化。整个小肠中甲硫氨酸脑啡肽含量明显降低，而十二指肠、回肠和盲肠中血管活性肠肽增加。P物质含量未受影响，而在疾病后期整个小肠中P物质含量显著降低。十二指肠中交感去甲肾上腺素和内源性血清素含量显著增加，肠道其余部分则无变化。这些数据表明，小肠和盲肠可能是糖尿病自主神经病变的早期靶点，后期可能会逐渐累及大肠其余部分，正如最近的研究结果所示。糖尿病患者中经常出现的胃肠功能障碍可能也归因于联合的突触前改变，以及最近报道的Gs与Gi/Go转导蛋白之间的功能失衡。在四氧嘧啶治疗七天后开始的胰岛素治疗，显著降低了高血糖，恢复了正常的身体生长，并预防了与四氧嘧啶诱导的糖尿病相关的所有肠道神经化学变化。
