Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion.
Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion.
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作者：
Osundiji MA;Lam DD;Shaw J;Yueh CY;Markkula SP;Hurst P;Colliva C;Roda A;Heisler LK;Evans ML
当患者从健康状况下降到2型糖尿病时，葡萄糖刺激胰岛素分泌（GSIS）通常会受到损害。虽然GSIS主要是由胰腺β细胞对血糖升高的直接感知驱动的，但越来越多的证据表明下丘脑神经元控制着外周葡萄糖代谢的其他方面。在这里，我们研究了大脑在GSIS的调节中的作用。为了研究下丘脑葡萄糖感知增加或减少对葡萄糖耐量和胰岛素分泌的影响，在静脉葡萄糖耐量试验（ivgts）期间分别向第三脑室注入葡萄糖或葡萄糖激酶抑制剂。葡萄糖输注的大鼠表现出改善的葡萄糖处理，特别是在IVGTT的前几分钟，在前10分钟（AUC0-10）内，偏移曲线下的面积显着降低。这可以用胰岛素分泌增加来解释。相比之下，输注葡萄糖激酶抑制剂葡萄糖胺或甘露庚糖会使葡萄糖耐量恶化，并在IVGTT的前几分钟降低GSIS。我们的数据表明，脑葡萄糖传感器在GSIS的调节中起作用，特别是在早期阶段。我们提出，针对下丘脑葡萄糖感应通路的药物可能代表了增强2型糖尿病早期胰岛素分泌的新治疗策略。
As patients decline from health to type 2 diabetes, glucose-stimulated insulin secretion (GSIS) typically becomes impaired. Although GSIS is driven predominantly by direct sensing of a rise in blood glucose by pancreatic β-cells, there is growing evidence that hypothalamic neurons control other aspects of peripheral glucose metabolism. Here we investigated the role of the brain in the modulation of GSIS. To examine the effects of increasing or decreasing hypothalamic glucose sensing on glucose tolerance and insulin secretion, glucose or inhibitors of glucokinase, respectively, were infused into the third ventricle during intravenous glucose tolerance tests (IVGTTs). Glucose-infused rats displayed improved glucose handling, particularly within the first few minutes of the IVGTT, with a significantly lower area under the excursion curve within the first 10 min (AUC0-10). This was explained by increased insulin secretion. In contrast, infusion of the glucokinase inhibitors glucosamine or mannoheptulose worsened glucose tolerance and decreased GSIS in the first few minutes of IVGTT. Our data suggest a role for brain glucose sensors in the regulation of GSIS, particularly during the early phase. We propose that pharmacological agents targeting hypothalamic glucose-sensing pathways may represent novel therapeutic strategies for enhancing early phase insulin secretion in type 2 diabetes.
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DOI：
10.1016/j.vascn.2007.12.002
发表时间：
2008-03-01
影响因子：
1.9
作者：
Frangioudakis, Georgia;Gyte, Amie C.;Poucher, Simon M.
通讯作者：
Poucher, Simon M.
影响因子：
9.8
作者：
Gredell, JA;Turnquist, PA;Pearce, RA
通讯作者：
Pearce, RA
影响因子：
56.9
作者：
Grimsby, J;Sarabu, R;Grippo, JF
通讯作者：
Grippo, JF
影响因子：
15.9
作者：
PORTE, D;GIRARDIER, L;POSTERNAK, J
通讯作者：
POSTERNAK, J
DOI：
10.1073/pnas.89.7.2619
发表时间：
1992-04-01
影响因子：
11.1
作者：
JETTON, TL;MAGNUSON, MA
通讯作者：
MAGNUSON, MA