GIP-Dependent Expression of Hypothalamic Genes
GIP-Dependent Expression of Hypothalamic Genes
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DOI：
10.33549/physiolres.932151
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发表时间：
2011-01-01
影响因子：
2.1
通讯作者：
Baile, C. A.
中科院分区：
文献类型：
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作者：
Ambati, S.;Duan, J.;Baile, C. A.
GIP（葡萄糖依赖性促胰岛素多肽）最初被鉴定为在肠道中合成的肠促胰岛素肽，最近已在脑中鉴定出其沿着其受体（GIPR）。我们的目的是研究GIP在下丘脑基因表达中的作用，这些基因表达与调节能量平衡和摄食行为相关的神经回路有关。用侧脑室插管的大鼠每天给予10 μ g GIP或10 μ l人工脑脊液（SF），持续4天，之后收集整个下丘脑。真实的时间Taqrnan（TM）RT-PCR用于定量比较下丘脑中一组基因的mRNA表达水平。GIP可上调下丘脑AVP mRNA水平（46.9 +/-4.5%），CART（25.9 +/-2.7%），CREB 1（38.5 +/-4.5%），GABRD（67.1 +/-11%），JAK 2（22.1 ± 3.6%）、MAPK 1（33.8 ± 7.8%）、NPY（25.3 ± 5.3%）、OXT（49.1 ± 5.1%）、STAT 3（21.6 ± 3.8%）和TH（33.9 ± 8.5%）。在第二个实验中，在GIPR（-/-）和GIPR（+/？）小鼠以确定缺乏GIP刺激对基因表达的影响。在GIPR（-/-）小鼠中，以下基因的表达下调：AVP（27.1 +/-7.5%）、CART（28.3 +/-3.7%）、OXT（25.2 +/-5.8%）、PTGES（23.9 +/-4.5%）和STAT 3（8.8 +/-2.3%）。提示AVP、CART、OXT和STAT 3可能参与了GIP对下丘脑能量平衡相关回路的影响。
GIP (glucose dependent insulinotrophic polypeptide), originally identified as an incretin peptide synthesized in the gut, has recently been identified, along with its receptors (GIPR), in the brain. Our objective was to investigate the role of GIP in hypothalamic gene expression of biomarkers linked to regulating energy balance and feeding behavior related neurocircuitry. Rats with lateral cerebroventricular cannulas were administered 10 mu g GIP or 10 mu l artificial cerebrospinal fluid (SF) daily for 4 days, after which whole hypothalami were collected. Real time Taqrnan (TM) RT-PCR was used to quantitatively compare the mRNA expression levels of a set of genes in the hypothalamus. Administration of GIP resulted in up-regulation of hypothalamic mRNA levels of AVP (46.9 +/- 4.5 %), CART (25.9 +/- 2.7 %), CREB1 (38.5 +/- 4.5 %), GABRD (67.1 +/- 11 %), JAK2 (22.1 +/- 3.6 %), MAPK1 (33.8 +/- 7.8 %), NPY (25.3 +/- 5.3 %), OXT (49.1 +/- 5.1 %), STAT3 (21.6 +/- 3.8 %), and TH (33.9 +/- 8.5 %). In a second experiment the same set of genes was evaluated in GIPR(-/-) and GIPR(+/?) mice to determine the effect of lack of GIP stimulation on gene expression. In GIPR(-/-) mice expressions of the following genes were down-regulated: AVP (27.1 +/- 7.5 %), CART (28.3 +/- 3.7 %), OXT (25.2 +/- 5.8 %), PTGES (23.9 +/- 4.5 %), and STAT3 (8.8 +/- 2.3 %). These results suggest that AVP, CART, OXT and STAT3 may be involved in energy balance-related hypothalamic circuits affected by GIP.