Page 47 - 南京医科大学学报自然科学版

第41卷第5期 南京医科大学学报（自然科学版）
2021年5月 Journal of Nanjing Medical University（Natural Sciences） ·677 ·

·临床医学·

IVGTT过程中血糖及胰岛素急遽波动对血清PCSK9水平的影响

陆晨妍，龚颖芸 ，付真真，顾经宇，周红文 *
*
南京医科大学第一附属医院内分泌科，江苏 南京 210029

［摘 要］ 目的：研究静脉葡萄糖耐量试验（intravenous glucose tolerance test，IVGTT）过程中血糖及胰岛素急遽波动对血清前
蛋白转化酶枯草溶菌素9（proprotein convertase subtilisin/kexin type 9，PCSK9）水平的影响，及其与机体糖脂代谢之间的潜在关
联。方法：对23例健康志愿者及52例肥胖或糖代谢异常患者进行病史采集、人体测量学、肝肾功能等及IVGTT检查，根据PC⁃
SK9在静脉葡萄糖负荷后4 min与0 min时的比值界定下降组、稳定组与上升组，并比较3组在各项糖脂代谢指标间的差异。进
一步对39例留取的血清样本使用高通量靶向脂质组学测定游离脂肪酸、神经酰胺及其代谢产物含量，比较上述各组的差异。
结果：总体基线PCSK9水平与总胆固醇、空腹C肽水平经校正后存在正相关关系，但与空腹胰岛素水平无显著相关性。随着
IVGTT 过程中血糖升高导致胰岛素急遽上升，伴随血清PCSK9水平波动，血清PCSK9在60 min后基本恢复至基线水平。PC⁃
SK9下降组的基础PCSK9及空腹胰岛素水平显著高于稳定组与上升组，且PCSK9下降组糖尿病前期与糖尿病者占比更高。此
外，下降组血清总神经酰胺、总葡糖神经酰胺水平也明显高于其他两组；脂质亚类分析显示，基线PCSK9含量与Cer d18：1/24：
0、GM3 d18：0/24：0在校正其他因素后正相关性仍存在。结论：IVGTT过程中血糖升高导致胰岛素急遽上升，伴随血清PCSK9
水平波动；波动模式受基线糖脂代谢状态影响。
［关键词］ PCSK9；静脉葡萄糖耐量；胰岛素；神经酰胺
［中图分类号］ R587.1 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）05⁃677⁃07
doi：10.7655/NYDXBNS20210507

The effects of abrupt fluctuation of blood glucose and insulin on serum PCSK9 level
during IVGTT

*
LU Chenyan，GONG Yingyun*，FU Zhenzhen，GU Jingyu，ZHOU Hongwen
Department of Endocrinology and Metabolism，the First Affiliated Hospital of Nanjing Medical University，Nanjing
210029，China

［Abstract］ Objective：This study aims to investigate the influence of abrupt fluctuation of blood glucose and insulin on serum
PCSK9 level during intravenous glucose tolerance test（IVGTT），and its potential relationship with glucose and lipid metabolism.
Methods：IVGTT were detected on 23 healthy lean and 52 patients with obesity or abnormal glucose metabolism. Personal medical
history and anthropometry were recorded. Lipid profile，liver function and kidney function were measured in fasting serum samples.
Serum PCSK9 levels were detected in serum samples collected during IVGTT at different time points. According to the ratio of serum
PCSK9 content between 4 minutes post intravenous glucose challenge and baseline，participants were grouped into the down⁃regulation
group，the stable group and the up ⁃ regulation group. Glucose and lipid metabolism parameters were compared across these three
groups. Besides，free fatty acids，ceramides and their metabolites in 39 serum samples were determined by high throughput targeting
lipidomics. Results：In general，baseline PCSK9 level was positively correlated with total cholesterol and fasting C⁃peptide level after
adjustment，but basal PCSK9 level was not corrected with fasting insulin level. With the increase of blood glucose during IVGTT，
insulin increased sharply，accompanied by the fluctuation of serum PCSK9 level. The results showed that the basal PCSK9 and fasting
insulin levels in the down⁃regulation group were significantly higher than those in the stable group and the up⁃regulation group，and the
proportion of prediabetes and diabetes in the down⁃regulation group was higher. In addition，the serum levels of total ceramide and total
glucosylceramide in the down⁃regulation group were significantly higher than those in the other two groups. The positive correlation

［基金项目］ 国家自然科学基金项目（81670723，31900832）；江苏省科技厅自然科学青年基金项目（BK20191074）
∗
通信作者（Corresponding author），E⁃mail：gongyingyun@njmu.edu.cn；drhongwenzhou@njmu.edu.cn