Estrogenic stimulation of hypothalamic-limbic system metabolism in ageing diabetic C57BL/KsJ mice
Estrogenic stimulation of hypothalamic-limbic system metabolism in ageing diabetic C57BL/KsJ mice
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DOI：
10.1159/000054445
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发表时间：
1999-06-01
影响因子：
4.1
通讯作者：
Garris, DR
中科院分区：
文献类型：
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作者：
Garris, DR
对8-20周龄C57BL/KSJ正常(+/？)的雌性C57BL/KSJ正常(+/？)和糖尿病(db/db)小鼠，在3周龄开始用油(油：0.1毫升)或雌二醇(E：1微克/3.5天)治疗后，随后在8、12、16和20周龄测定RBGU率。在8到20周期间，所有对照组(油组和E组)的大脑葡萄糖利用率的基础比率都逐渐下降。高血糖-肥胖糖尿病综合征在db/db小鼠中的表达导致8至20周的RBGU比率与对照组相比显著降低。在雌激素敏感的下丘脑、隔区和杏仁体区域，与油剂治疗的糖尿病患者相比，E疗法调节了db/db小鼠的RBGU比率，但没有显著改变+/？老鼠。在皮质样本中，E疗法对对照组或糖尿病组的葡萄糖利用率没有显著影响。成熟期相关的中枢神经系统葡萄糖利用率在所有脑区的显著下降模式导致所有组在20周龄时表现出类似的区域代谢指数，除了油处理db/db组中糖尿病相关的RBGU比率的恶化。这些数据表明，糖尿病综合征加速了正常发育相关的局部大脑碳水化合物代谢的下降，E疗法可以调节激素敏感的中枢神经系统基因座上与发育相关的葡萄糖利用抑制。这些数据表明，糖尿病综合征对大脑碳水化合物利用率的抑郁影响可能在拥有类固醇隔离、代谢反应神经元的公认中枢神经系统区域得到治疗上的改善。
The therapeutic influences of estrogen treatment on age-and diabetes-related declines in regional brain glucose utilization (RBGU) rates were evaluated in 8- to 20-week-old female C57BL/KsJ normal (+/?) and diabetic (db/db) mice, Following either oil vehicle (oil: 0.1 ml) or estradiol (E: 1 mu g/3.5 days) treatments starting at 3 weeks of age, RBGU rates were subsequently determined at 8, 12, 16 and 20 weeks of age. A gradual decline in the basal rate of brain glucose utilization was observed in all control (oil- and E-treated) groups between 8 and 20 weeks. Expression of the hyperglycemic-obese diabetes syndrome in db/db mice resulted in a significant reduction in RBGU rates between 8 and 20 weeks relative to control values. In estrogen-sensitive hypothalamic, septal and amygdaloid regions, E therapy modulated RBGU rates in db/db mice relative to oil-treated diabetics, but did not significantly alter utilization rates in +/? mice. In cortical samples, E therapy had no significant influence on glucose utilization rates in either control or diabetic groups. A noticeable pattern of maturation-associated decline in CNS glucose utilization rates in all brain regions resulted in comparable regional metabolic indices being exhibited by all groups at 20 weeks of age, with the exception of the diabetes-associated exacerbation of RBGU rates in the oil-treated db/db group. These data demonstrate that the normal development-related decline in regional brain carbohydrate metabolism is accelerated by the diabetes syndrome, and that E therapy can modulate the syndrome-associated suppression of glucose utilization in steroid-sensitive CNS loci. These data suggest that the depressive influences of the diabetes syndrome on brain carbohydrate utilization rates may be therapeutically modified in recognized CNS regions possessing steroid-sequestering, metabolically responsive neurons.