The response of glucose-excited neurones in the ventromedial hypothalamus to decreased glucose is enhanced in a murine model of type 2 diabetes mellitus.
The response of glucose-excited neurones in the ventromedial hypothalamus to decreased glucose is enhanced in a murine model of type 2 diabetes mellitus.
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DOI：
10.1111/j.1365-2826.2009.01938.x
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发表时间：
2010-02
影响因子：
3.2
通讯作者：
Routh VH
中科院分区：
文献类型：
--
作者：
Cotero VE;Zhang BB;Routh VH
肥胖和 2 型糖尿病 (T2DM) 与胰岛素信号传导功能障碍和中枢葡萄糖感应受损有关。葡萄糖传感神经元位于大脑中参与葡萄糖和能量稳态的关键区域（例如下丘脑腹内侧区；VMH）。我们最近发现，胰岛素会减弱葡萄糖兴奋（GE）神经元感知血糖下降的能力。我们假设，在 T2DM 期间，当胰岛素信号传导功能失调时，胰岛素对 VMH GE 神经元的这种作用就会受损。为了检验我们的假设，我们使用全细胞膜片钳记录技术来评估胰岛素对野生型和糖尿病 (db/db) 小鼠脑切片中 VMH GE 神经元的影响。在野生型和 db/db 小鼠中，将葡萄糖从 2.5 mm 降低至 0.1 mm 对 VMH GE 神经元的影响相似。然而，与野生型小鼠相比，将 db/db 小鼠中的葡萄糖从 2.5 mm 降低至 0.5 mm 会显着更大程度地降低 VMH GE 神经元的动作电位频率、膜电位和输入电阻。此外，胰岛素 (5 nm) 可以减弱野生型小鼠血糖下降的影响，但不能减弱 db/db 小鼠的血糖下降效果。野生型小鼠和 db/db 小鼠之间葡萄糖和胰岛素敏感性的这些差异被胰岛素增敏剂化合物 2 (300 nm) 完全改善。这些数据与我们的假设一致，即 T2DM 中胰岛素信号受损会使 VMH GE 神经元对葡萄糖降低敏感。
Obesity and type 2 diabetes mellitus (T2DM) are associated with dysfunctional insulin signalling and impaired central glucose sensing. Glucose sensing neurones reside in key areas of the brain involved in glucose and energy homeostasis (e.g. ventromedial hypothalamus; VMH). We have recently shown that insulin attenuates the ability of glucose-excited (GE) neurones to sense decreased glucose. We hypothesise that this effect of insulin on VMH GE neurones is impaired during T2DM when insulin signalling is dysfunctional. To test our hypotheses, we used whole cell patch clamp recording techniques to evaluate the effects of insulin on VMH GE neurones in brain slices from wild-type and diabetic (db/db) mice. The effects of decreasing glucose from 2.5 to 0.1 mm on VMH GE neurones were similar in wild-type and db/db mice. However, decreasing glucose from 2.5 to 0.5 mm decreased the action potential frequency, membrane potential and input resistance of VMH GE neurones to a significantly greater extent in db/db versus wild-type mice. Furthermore, insulin (5 nm) blunted the effects of decreased glucose in wild-type, but not db/db mice. These differences in both glucose and insulin sensitivity between wild-type and db/db mice were completely ameliorated by the insulin sensitiser, Compound 2 (300 nm). These data are consistent with our hypothesis that impaired insulin signalling in T2DM sensitises VMH GE neurones to decreased glucose.
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影响因子：
7.7
作者：
Song, ZT;Levin, BE;Routh, VH
通讯作者：
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DOI：
10.1152/ajpregu.00148.2006
发表时间：
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