DIARRHEA IN STREPTOZOCIN-TREATED RATS - LOSS OF ADRENERGIC REGULATION OF INTESTINAL FLUID AND ELECTROLYTE TRANSPORT
DIARRHEA IN STREPTOZOCIN-TREATED RATS - LOSS OF ADRENERGIC REGULATION OF INTESTINAL FLUID AND ELECTROLYTE TRANSPORT
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DOI：
10.1172/jci111874
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
FIELD, M
中科院分区：
文献类型：
--
作者：
CHANG, EB;BERGENSTAL, RM;FIELD, M
链脲佐菌素诱导的慢性糖尿病大鼠出现腹泻。这种腹泻的可能性是改变神经元控制水和电解质吸收肠上皮的结果进行了调查。去甲肾上腺素能控制被检查，因为。已知-2-肾上腺素能激动剂可刺激肠液吸收。与非糖尿病鼠相比，慢性糖尿病大鼠的回肠和结肠对液体的吸收明显受损，而空肠则没有。在胰岛素治疗或未治疗的急性糖尿病（7 d [day]）动物中均未发现这种肠液吸收损伤。各组粘膜组织学均正常。通过体外对酪胺的短路电流（Isc）反应，估计慢性糖尿病大鼠空肠和回肠粘膜去甲肾上腺素的储存。添加Pargyline是为了抑制添加的酪胺的酶破坏。在慢性糖尿病大鼠中，Isc对酪胺的反应在回肠中显著降低，但在空肠中没有。当这些反应被表达为Isc组织对外源性肾上腺素最大反应的一部分时，回肠和空肠的反应都显著降低。在急性糖尿病大鼠的组织中，Isc对酪胺和肾上腺素的反应与对照组没有什么不同。当用6- oh -多巴胺治疗非糖尿病大鼠产生交感神经去神经时，液体吸收受损的模式与慢性糖尿病大鼠观察到的相同。链脲佐菌素致糖尿病的大鼠肠粘膜对液体和电解质的吸收受损，这是由于正常情况下肠细胞的去甲肾上腺素能神经支配的丧失。
Diarrhea was noted in rats with streptozocin-induced chronic diabetes. The possibility that this diarrhea is a consequence of altered neuronal control of H2O and electolyte absorption in the intestinal epithelium was investigated. Noradrenergic control was examined because .alpha.-2-adrenergic agonists are known to stimulate intestinal fluid absorption. When compared with nondiabetic littermates, chronically diabetic rats exhibited significant impairement of fluid absorption by the ileum and colon, but not the jejunum. This impairment of intestinal fluid absorption was not found in either insulin-treated or untreated acutely diabetic (7 d [day]) animals. Mucosal histology appeared normal in all of the above groups. Mucosal norepinephrine stores in the jejunum and ileum of chronically diabetic rats were estimated in vitro by the short-circuit current (Isc) response to tyramine, an agent that effectively releases stored norepinephrine. Pargyline was added to inhibit enzymatic destruction of the added tyramine. In chronically diabetic rats, the Isc response to tyramine was significantly decreased in ileum, but not in jejunum. When these responses were expressed as a fraction of the maximal Isc tissue response to exogenously added epinephrine, significant decreases were noted in both ileum and jejunum. In tissues from acutely diabetic rats, Isc responses to tyramine and epinephrine were no different from controls. When sympathetic denervation was produced in nondiabetic rats by treatment with 6-OH-dopamine, the pattern of impaired fluid absorption that developed was the same as that observed in chronically diabetic rats. Impaired intestinal mucosal absorption of fluid and electrolytes slowly develops in rats made diabetic with streptozocin and that this absorptive impairment is due to a loss of normally present noradrenergic innervation of enterocytes.