Chang E B, Bergenstal R M, Field M
J Clin Invest. 1985 May;75(5):1666-70. doi: 10.1172/JCI111874.
Diarrhea was noted in rats with streptozocin-induced chronic diabetes. We have investigated the possibility that this diarrhea is a consequence of altered neuronal control of water and electrolyte absorption in the intestinal epithelium. In particular, we examined noradrenergic control because alpha-2-adrenergic agonists are known to stimulate intestinal fluid absorption. When compared with nondiabetic littermates, chronically diabetic rats exhibited significant impairment 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) 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. However, 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. We conclude that 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.
链脲佐菌素诱导的慢性糖尿病大鼠出现腹泻。我们研究了这种腹泻是否是肠道上皮水和电解质吸收的神经控制改变所致。特别是，我们检查了去甲肾上腺素能控制，因为已知α-2-肾上腺素能激动剂可刺激肠道液体吸收。与非糖尿病同窝仔鼠相比，慢性糖尿病大鼠回肠和结肠的液体吸收明显受损，但空肠未受影响。在胰岛素治疗或未治疗的急性糖尿病（7天）动物中均未发现这种肠道液体吸收受损情况。上述所有组的黏膜组织学均正常。通过对酪胺（一种有效释放储存去甲肾上腺素的药物）的短路电流（Isc）反应，体外估计慢性糖尿病大鼠空肠和回肠的黏膜去甲肾上腺素储存量。加入帕吉林以抑制添加的酪胺的酶促破坏。在慢性糖尿病大鼠中，回肠对酪胺的Isc反应明显降低，但空肠未降低。然而，当这些反应表示为对外源性添加肾上腺素的最大Isc组织反应的分数时，回肠和空肠均出现明显降低。在急性糖尿病大鼠的组织中，对酪胺和肾上腺素的Isc反应与对照组无差异。当用6-OH-多巴胺治疗使非糖尿病大鼠产生交感神经去神经支配时，出现的液体吸收受损模式与慢性糖尿病大鼠中观察到的相同。我们得出结论，链脲佐菌素诱导的糖尿病大鼠中，肠道黏膜对液体和电解质的吸收受损是缓慢发展的，并且这种吸收受损是由于肠细胞正常存在的去甲肾上腺素能神经支配丧失所致。
