Reduced carnitine level causes death from hypoglycemia: Possible involvement of suppression of hypothalamic orexin expression during weaning period
Reduced carnitine level causes death from hypoglycemia: Possible involvement of suppression of hypothalamic orexin expression during weaning period
复制标题
DOI：
10.1507/endocrj.k07-044
复制
发表时间：
2007-12-01
影响因子：
2
通讯作者：
Kido, Hiroshi
中科院分区：
文献类型：
--
作者：
Kuwajima, Masamichi;Fujihara, Hiroaki;Kido, Hiroshi
肉碱缺乏症患者发生低血糖的机制尚未确定。使用全身性肉毒碱缺乏的小鼠（JVS小鼠），我们研究了这种机制，重点是断奶期（产后14-28天）。对于正常小鼠，存活率为100%，并且根本没有观察到低血糖。胃乳糖在第17天开始减少，纤维素含量在此后急剧增加。对于JVS小鼠，存活率在第14天为77%，在第28天为28%。从第21天开始，观察到低血糖。到第17天，胃乳糖几乎完全消失，从第14天到第28天几乎检测不到纤维素。在第14天，JVS和正常小鼠下丘脑中食欲素mRNA的表达没有差异，但在第21天和第28天，JVS小鼠下丘脑中食欲素mRNA的表达受到抑制。当JVS小鼠喂食富含肉毒碱的饮食时，下丘脑中食欲素mRNA表达的抑制被消除，并且在第28天在胃中检测到乳糖和纤维素，没有低血糖。总之，在断奶期间下丘脑食欲素表达的抑制可能参与了JVS小鼠明显的厌食症，最终导致低血糖死亡。
The mechanism of onset of hypoglycemia in patients with carnitine deficiency has yet to be determined. Using mice with systemic carnitine deficiency (JVS mice), we examined this mechanism, focusing on the weaning period (days 14-28 postpartum). For normal mice, the survival rate was 100%, and no hypoglycemia was observed at all. Gastric lactose began to decrease on day 17, and cellulose increased sharply in amount thereafter. For JVS mice, the survival rate was 77% on day 14 and 28% on day 28. From day 21 on, hypoglycemia was noted. Gastric lactose had disappeared almost completely by day 17, and cellulose was almost undetectable from days 14 to 28. Expression of orexin mRNA in the hypothalamus did not differ between JVS and normal mice on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mice were fed a carnitine-rich diet, suppression of expression of orexin mRNA in hypothalamus was eliminated, and on day 28 lactose and cellulose were detected in the stomach without hypoglycemia. In conclusion, the suppression of the expression of orexin in the hypothalamus during the weaning period may be involved in the marked anorexia in JVS mice, which eventually leads to death from hypoglycemia.