Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo.
Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo.
复制标题
下丘脑神经胶质细胞中的葡萄糖转运蛋白1介导葡萄糖传感，以调节体内葡萄糖的产生。
作者：
Chari M;Yang CS;Lam CK;Lee K;Mighiu P;Kokorovic A;Cheung GW;Lai TY;Wang PY;Lam TK
在正常的啮齿动物和人类中，循环葡萄糖抑制葡萄糖的产生，但在糖尿病中，这种葡萄糖的有效性被破坏，部分原因是持续的高血糖。我们假设糖尿病患者的高血糖会损害下丘脑对葡萄糖的感知，从而降低葡萄糖的产生，而下丘脑胶质细胞中葡萄糖转运蛋白-1 （GLUT1）的变化是体内高血糖的有害作用的原因。我们测试了下丘脑葡萄糖对链脲佐菌素（STZ）诱导的大鼠下丘脑葡萄糖浓度升高和葡萄糖产量降低的有效性，STZ和苯酞素诱导的糖尿病，以及全身和下丘脑持续高血糖。接下来，我们评估了下丘脑中胶质细胞GLUT1的含量，产生了一种由胶质纤维酸性蛋白（GFAP）启动子驱动的表达GLUT1的腺病毒（Ad-GFAP-GLUT1），并将Ad-GFAP-GLUT1注射到高血糖大鼠的下丘脑。胰正糖钳和示踪剂稀释方法用于评估体内葡萄糖动力学的变化。持续高血糖，如stz诱导的糖尿病早期发作，破坏下丘脑葡萄糖感知，增加下丘脑葡萄糖浓度，降低葡萄糖产量，与体内大鼠下丘脑胶质细胞中GLUT1水平降低相关。在stz诱导的GLUT1急性归一化血糖水平降低的大鼠和选择性诱导的下丘脑高血糖大鼠中，下丘脑胶质GLUT1的过表达恢复了下丘脑葡萄糖的有效性。持续高血糖会损害下丘脑的葡萄糖感知，通过改变下丘脑胶质GLUT1来降低葡萄糖的产生，这些数据强调了下丘脑胶质GLUT1在介导葡萄糖感知调节葡萄糖产生中的关键作用。
Circulating glucose inhibits glucose production in normal rodents and humans, but this glucose effectiveness is disrupted in diabetes due partly to sustained hyperglycemia. We hypothesize that hyperglycemia in diabetes impairs hypothalamic glucose sensing to lower glucose production, and changes of glucose transporter-1 (GLUT1) in the hypothalamic glial cells are responsible for the deleterious effects of hyperglycemia in vivo. We tested hypothalamic glucose effectiveness to increase hypothalamic glucose concentration and lower glucose production in rats induced with streptozotocin (STZ) uncontrolled diabetes, STZ and phlorizin, and whole-body and hypothalamic sustained hyperglycemia. We next assessed the content of glial GLUT1 in the hypothalamus, generated an adenovirus expressing GLUT1 driven by a glial fibrillary acidic protein (GFAP) promoter (Ad-GFAP-GLUT1), and injected Ad-GFAP-GLUT1 into the hypothalamus of rats induced with hyperglycemia. Pancreatic euglycemic clamp and tracer-dilution methodologies were used to assess changes in glucose kinetics in vivo. Sustained hyperglycemia, as seen in the early onset of STZ-induced diabetes, disrupted hypothalamic glucose sensing to increase hypothalamic glucose concentration and lower glucose production in association with reduced GLUT1 levels in the hypothalamic glial cells of rats in vivo. Overexpression of hypothalamic glial GLUT1 in STZ-induced rats with reduced GLUT1 acutely normalized plasma glucose levels and in rats with selectively induced hypothalamic hyperglycemia restored hypothalamic glucose effectiveness. Sustained hyperglycemia impairs hypothalamic glucose sensing to lower glucose production through changes in hypothalamic glial GLUT1, and these data highlight the critical role of hypothalamic glial GLUT1 in mediating glucose sensing to regulate glucose production.