Neuroprotection by glucagon: role of gluconeogenesis.
Neuroprotection by glucagon: role of gluconeogenesis.
复制标题
DOI：
10.3171/2010.4.jns10263
复制
发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Higazi, Abd Al-Roof
中科院分区：
文献类型：
--
作者：
Fanne, Rami Abu;Nassar, Taher;Higazi, Abd Al-Roof
目的：创伤性脑损伤（TBI）后神经功能缺损的严重程度会因几种内源性过程而加剧，包括高血糖症、低血压和谷氨酸盐的产生。然而，除了控制高血糖症，胰岛素对组织代谢具有多效性作用，包括降低神经毒性氨基酸谷氨酸的浓度，使得胰岛素的有益作用是否归因于自身的eukaryotic的建立尚不清楚。在本研究中，作者询问，如果减少谷氨酸通过的方法，不降低葡萄糖水平将改善神经系统的结果TBI.METHODS：胰高血糖素激活肝再生增加的氨基酸，如谷氨酸的摄取，并促进其转化为葡萄糖。胰高血糖素在闭合性脑损伤（CHI）之前或之后作为单次腹膜内注射给药。神经功能，脑组织学特征，血谷氨酸和葡萄糖水平，和CSF谷氨酸concentration.RESULTS：一个单一的腹腔注射胰高血糖素（25 μ g）到小鼠10分钟之前或之后CHI减少病变大小约60%（p < 0.0001）和加速神经恢复。胰高血糖素的神经保护作用与神经再生有关，其通过将循环中神经兴奋性氨基酸谷氨酸的浓度从未治疗小鼠的207 ± 32.1 mumol/L降低至治疗小鼠的101.11 ± 21.6 mumol/L（p < 0.001）;在CSF中也发生了类似的作用。胰高血糖素的神经保护作用，尽管随之而来的血糖增加，最终底物的mesogenesization.CONCLUSIONS：胰高血糖素发挥显着的神经保护作用后，TBI降低中枢神经系统谷氨酸。胰高血糖素是有益的，尽管增加血糖。当胰高血糖素在TBI之前给予时也发生有利的作用，表明其参与预处理过程。因此，胰高血糖素在TBI后或在围手术期缺血发生率高的某些神经外科或心脏介入治疗前给药时，可能具有提供神经保护的价值。
OBJECT: The severity of neurological impairment following traumatic brain injury (TBI) is exacerbated by several endogenous processes, including hyperglycemia, hypotension, and the generation of glutamate. However, in addition to controlling hyperglycemia, insulin has pleiotropic effects on tissue metabolism, which include reducing the concentration of the neurotoxic amino acid glutamate, making it unclear whether insulin's beneficial effects are attributable to the establishment of euglycemia per se. In the present study, the authors asked if reducing glutamate via approaches that do not lower glucose levels would improve neurological outcome following TBI.METHODS: Glucagon activates gluconeogenesis by increasing the hepatic uptake of amino acids such as glutamate and facilitating their conversion to glucose. Glucagon was administered as a single intraperitoneal injection before or after closed head injury (CHI). Neurological function, brain histological features, blood glutamate and glucose levels, and CSF glutamate concentrations were measured.RESULTS: A single intraperitoneal injection of glucagon (25 mug) into mice 10 minutes before or after CHI reduced lesion size by about 60% (p < 0.0001) and accelerated neurological recovery. The neuroprotective effect of glucagon was related to gluconeogenesis by decreasing the concentration of the neuroexcitatory amino acid glutamate in the circulation from 207 ± 32.1 mumol/L in untreated mice to 101.11 ± 21.6 mumol/L in treated mice (p < 0.001); a similar effect occurred in the CSF. The neuroprotective effect of glucagon was seen notwithstanding the attendant increase in blood glucose, the final substrate of gluconeogenesis.CONCLUSIONS: Glucagon exerts a marked neuroprotective effect post-TBI by decreasing CNS glutamate. Glucagon was beneficial despite increasing blood glucose. Favorable effects also occurred when glucagon was given prior to TBI, suggesting its involvement in the preconditioning process. Thus, glucagon may be of value in providing neuroprotection when administered after TBI or prior to certain neurosurgical or cardiac interventions in which the incidence of perioperative ischemia is high.