Zelena Dóra, Mergl Zsuzsa, Makara Gábor B
Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Szigony 43, Hungary.
Brain Res Bull. 2006 Mar 15;69(1):48-56. doi: 10.1016/j.brainresbull.2005.10.009. Epub 2005 Nov 9.
Chronic diabetes mellitus (DM) induces hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA). Our present study addresses the role of vasopressin (AVP) in maintaining adrenocortical responsiveness during DM. AVP-deficient mutant Brattleboro rats were used with heterozygous controls and the V2 agonist, desmopressin was infused to replace peripheral AVP. To induce DM the rats were injected by streptozotocin (STZ, 60 mg/ml/kg i.v.) and studied 2 weeks later. The acute stress stimulus was 60 min restraint. The signs of DM (the increase in water consumption and in blood glucose levels) were discovered in all rats. The diuretic effect of the lack of AVP was additional to the DM-induced osmotic diuresis. DM induced significant, chronic stress-like somatic changes on which AVP-deficiency had no effect and although desmopressin infusion normalized the water consumption and the body weight gain in AVP-deficient rats, it had no effect on DM-induced changes. The acute stress-induced plasma ACTH elevation was smaller in AVP-deficient or DM rats but these effects were not additive. Desmopressin did not normalize the decreased ACTH-elevation of AVP-deficient animals. The resting morning plasma corticosterone level was elevated both in DM and AVP-deficient rats without interaction. The restraint-induced corticosterone rise was influenced neither by the lack of AVP nor by DM and the basal and stress-induced prolactin levels were smaller in DM rats without any effect of AVP-deficiency. In conclusion, our data suggest that AVP does not play a crucial role in HPA axis regulation during DM-induced chronic stress. In contrast, the role of AVP seems to be more important during acute stress, however, it is restricted to the ACTH regulation. According to the water consumption data diabetes insipidus seems to be an additional risk factor for DM.
慢性糖尿病（DM）会导致下丘脑 - 垂体 - 肾上腺轴（HPA）功能亢进。我们目前的研究探讨了血管加压素（AVP）在糖尿病期间维持肾上腺皮质反应性中的作用。使用AVP缺乏的突变型布拉特洛维大鼠及其杂合子对照，并注入V2激动剂去氨加压素以替代外周AVP。为诱导糖尿病，给大鼠静脉注射链脲佐菌素（STZ，60mg/ml/kg），并在2周后进行研究。急性应激刺激为60分钟束缚。在所有大鼠中均发现了糖尿病的体征（饮水量和血糖水平升高）。AVP缺乏导致的利尿作用叠加在糖尿病诱导的渗透性利尿之上。糖尿病引起了显著的慢性应激样躯体变化，AVP缺乏对此没有影响，尽管注入去氨加压素使AVP缺乏大鼠的饮水量和体重增加恢复正常，但对糖尿病诱导的变化没有影响。急性应激诱导的血浆促肾上腺皮质激素（ACTH）升高在AVP缺乏或糖尿病大鼠中较小，但这些效应并非相加性的。去氨加压素未能使AVP缺乏动物降低的ACTH升高恢复正常。DM和AVP缺乏大鼠静息晨血浆皮质酮水平均升高，且无相互作用。束缚诱导的皮质酮升高既不受AVP缺乏影响，也不受糖尿病影响，糖尿病大鼠基础和应激诱导的催乳素水平较低，AVP缺乏对此无任何影响。总之，我们的数据表明，AVP在糖尿病诱导的慢性应激期间对HPA轴调节不起关键作用。相反，AVP在急性应激期间的作用似乎更重要，然而，它仅限于ACTH调节。根据饮水量数据，尿崩症似乎是糖尿病的一个额外危险因素。
