Glucose metabolism and pancreatic defects in spinal muscular atrophy.
Glucose metabolism and pancreatic defects in spinal muscular atrophy.
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DOI：
10.1002/ana.23582
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发表时间：
2012-08
影响因子：
11.2
通讯作者：
Kothary, Rashmi
中科院分区：
文献类型：
--
作者：
Bowerman, Melissa;Swoboda, Kathryn J.;Michalski, John-Paul;Wang, Gen-Sheng;Reeks, Courtney;Beauvais, Ariane;Murphy, Kelley;Woulfe, John;Screaton, Robert A.;Scott, Fraser W.;Kothary, Rashmi
脊髓性肌萎缩症（SMA）是幼儿的头号基因杀手。它是由存活运动神经元1 （SMN1）基因突变或缺失引起的。虽然SMA主要是一种运动神经元疾病，但代谢异常，如代谢性酸中毒、脂肪酸代谢异常、高脂血症和高血糖症已在SMA患者中报道。因此，我们开始了对SMA中葡萄糖代谢的深入分析。研究了Smn2B/−中间型SMA小鼠模型和I型SMA患者的糖代谢和胰腺发育。在这里，我们在SMA小鼠模型中证明了胰岛内细胞命运的严重不平衡，产生胰高血糖素的α细胞占主导地位，而产生胰岛素的β细胞则占主导地位。这些SMA小鼠表现出空腹高血糖、高胰高血糖素血症和葡萄糖抵抗。我们在患有严重婴儿型SMA的死亡儿童的胰岛中发现了类似的异常，并在这些儿童中至少有一部分存在葡萄糖耐受不良的支持性证据。我们的研究结果表明，葡萄糖代谢缺陷可能在SMA发病机制中起重要作用。
Spinal muscular atrophy (SMA) is the number 1 genetic killer of young children. It is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although SMA is primarily a motor neuron disease, metabolism abnormalities such as metabolic acidosis, abnormal fatty acid metabolism, hyperlipidemia, and hyperglycemia have been reported in SMA patients. We thus initiated an in-depth analysis of glucose metabolism in SMA. Glucose metabolism and pancreas development were investigated in the Smn2B/− intermediate SMA mouse model and type I SMA patients. Here, we demonstrate in an SMA mouse model a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon-producing α cells at the expense of insulin-producing β cells. These SMA mice display fasting hyperglycemia, hyperglucagonemia, and glucose resistance. We demonstrate similar abnormalities in pancreatic islets from deceased children with the severe infantile form of SMA in association with supportive evidence of glucose intolerance in at least a subset of such children. Our results indicate that defects in glucose metabolism may play an important contributory role in SMA pathogenesis.
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影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
2.2
作者：
Kim A;Miller K;Jo J;Kilimnik G;Wojcik P;Hara M
通讯作者：
Hara M
影响因子：
3.7
作者：
Liu Z;Kim W;Chen Z;Shin YK;Carlson OD;Fiori JL;Xin L;Napora JK;Short R;Odetunde JO;Lao Q;Egan JM
通讯作者：
Egan JM
影响因子：
--
作者：
DAHL, DS;PETERS, HA
通讯作者：
PETERS, HA
影响因子：
30.8
作者：
Lefebvre, S;Burlet, P;Melki, J
通讯作者：
Melki, J