Research on hypoglycemia caused by inhibition of orexin expression

肉碱缺乏症患者发生低血糖的机制尚未确定。我们使用系统性肉碱缺乏症小鼠（JVS小鼠）研究了这一机制，重点是断奶期（产后1428天）。正常小鼠存活率100%，无低血糖现象发生。胃乳糖在第17天开始减少，此后愈伤筋数量急剧增加。JVS小鼠第14天和第28天存活率分别为77%和28%。第21天开始出现低血糖。胃乳糖在第17天几乎完全消失，纤维素在第14至28天几乎检测不到。在第14天，JVS小鼠下丘脑中食欲素mRNA的表达与正常小鼠没有差异，但在第21和28天，JVS小鼠的食欲素mRNA表达受到抑制。饲喂富含肉毒碱的日粮，消除了下丘脑食欲素mRNA表达的抑制，第28天胃中检测到乳糖和纤维素，无低血糖。综上所述，断奶期下丘脑食欲素表达的抑制可能参与了JVS小鼠明显的厌食，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 1428 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 callulose 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 rake on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mire 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.