Effects of diabetes and insulin on the expression of galanin-like peptide in the hypothalamus of the rat
Effects of diabetes and insulin on the expression of galanin-like peptide in the hypothalamus of the rat
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DOI：
10.2337/diabetes.53.5.1237
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发表时间：
2004-05-01
期刊：
影响因子：
7.7
通讯作者：
Steiner, RA
中科院分区：
文献类型：
--
作者：
Fraley, GS;Scarlett, JM;Steiner, RA
甘丙肽样肽（Galanin-like peptide，GALP）是由下丘脑弓状核的一小部分神经元产生的，瘦素刺激下丘脑GALP mRNA的表达。由于胰岛素和瘦素在大脑中有着共同的信号通路，我们推断GALP神经元也可能对循环中胰岛素浓度的变化做出反应。为了验证这一假设，我们首先通过比较正常和糖尿病动物之间的GALP mRNA水平来研究胰岛素缺乏对GALP表达的影响。链脲佐菌素诱导的糖尿病与GALP mRNA表达的显著降低相关，而胰岛素或瘦素治疗可逆转GALP mRNA表达的降低。第二，我们研究了胰岛素直接注入大脑对禁食大鼠GALP mRNA表达的影响。禁食48小时后，动物下丘脑GALP mRNA水平较低，胰岛素中枢治疗可逆转这种效应。这些结果表明，GALP神经元是胰岛素调节的直接靶点，并暗示这些细胞在1型糖尿病的代谢和行为后遗症中发挥作用。
Galanin-like peptide (GALP) is produced in a small population of neurons in the arcuate nucleus of the hypothalamus, and leptin stimulates the hypothalamic expression of GALP mRNA. Because insulin and leptin share common signaling pathways in the brain, we reasoned that GALP neurons might also be responsive to changes in circulating concentrations of insulin. To test this hypothesis, we first studied the effect of insulin deficiency on the expression of GALP by comparing levels of GALP mRNA between normal and diabetic animals. Streptozotocin-induced diabetes was associated with a significant reduction in the expression of GALP mRNA, which was reversed by treatment with either insulin or leptin. Second, we examined the effect of insulin administered directly into the brain on the expression of GALP mRNA in fasted rats. Hypothalamic levels of GALP mRNA were lower in animals after a 48-h fast, and central treatment with insulin reversed this effect. These results suggest that GALP neurons are direct targets for regulation by insulin and implicate these cells for a role in the metabolic and behavioural sequelae of type 1 diabetes.