Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia
Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia
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DOI：
10.1016/j.cmet.2007.04.001
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发表时间：
2007-05-01
期刊：
影响因子：
29
通讯作者：
Lowell, Bradford B.
中科院分区：
文献类型：
--
作者：
Tong, Qingchun;Ye, ChianPing;Lowell, Bradford B.
神经肽在下丘脑中的重要性已经通过实验得到证实。由于难以评估体内功能，快速作用的神经递质谷氨酸和GABA的作用在很大程度上是未知的。突触囊泡转运蛋白（谷氨酸的VGLUT和GABA的VGAT）是囊泡摄取所必需的，因此，神经递质的突触释放。下丘脑腹内侧（VMH）神经元主要是丘脑能神经元，表达VGLUT 2。为了评估谷氨酸从VMH神经元释放的作用，我们产生了在SF 1神经元（VMH神经元的主要子集）中选择性缺乏VGLUT 2的小鼠。这些小鼠在禁食期间具有低血糖症，其继发于受损的禁食诱导的升糖胰腺激素胰高血糖素的增加和受损的肝脏中编码PGC-1 α和促胰岛素生成酶PEPCK和G6 β的ml的诱导。同样，这些小鼠对胰岛素诱导的低血糖和2-脱氧葡萄糖（一种抗代谢物）的反调节反应也有缺陷。因此，从VMH神经元释放谷氨酸是神经回路的重要组成部分，其功能是防止低血糖。
The importance of neuropeptides in the hypothalamus has been experimentally established. Due to difficulties in assessing function in vivo, the roles of the fast-acting neurotransmitters glutamate and GABA are largely unknown. Synaptic vesicular transporters (VGLUTs for glutamate and VGAT for GABA) are required for vesicular uptake and, consequently, synaptic release of neurotransmitters. Ventromedial hypothalamic (VMH) neurons are predominantly glutamatergic and express VGLUT2. To evaluate the role of glutamate release from VMH neurons, we generated mice lacking VGLUT2 selectively in SF1 neurons (a major subset of VMH neurons). These mice have hypoglycemia during fasting secondary to impaired fasting-induced increases in the glucose-raising pancreatic hormone glucagon and impaired induction in liver of ml encoding PGC-1 alpha and the gluconeogenic enzymes PEPCK and G6Pase. Similarly, these mice have defective counterregulatory responses to insulin-induced hypoglycemia and 2-deoxyglucose (an antimetabolite). Thus, glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia.