Pendharkar Sayali A, Drury Marie, Walia Monika, Korc Murray, Petrov Maxim S
Department of Surgery, University of Auckland, Auckland, New Zealand.
Department of Medicine, Biochemistry and Molecular Biology, Division of Endocrinology, Indiana University School of Medicine, the Melvin and Bren Simon Cancer Center and the Pancreatic Cancer Signature Centre, Indianapolis, IN, USA.
Gastroenterology Res. 2017 Aug;10(4):224-234. doi: 10.14740/gr890w. Epub 2017 Aug 31.
Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis.
Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors.
A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant.
GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro-inflammatory cytokines, as well as certain pancreatic and gut hormones. Detailed mechanistic studies are now warranted to investigate the exact role of GRP in derangements of glucose homeostasis following pancreatitis.
胃泌素释放肽（GRP）是一种多能肽，与胃肠道炎症状态以及糖尿病等经典慢性代谢疾病均有关联。胰腺炎是一种累及胃肠道的典型炎症性疾病，胰腺炎后的异常糖代谢（AGM）与持续性低度炎症以及胰腺和肠道激素及细胞因子分泌改变有关。虽然GRP参与其中多种物质的分泌，但尚不清楚GRP在AGM中是否发挥作用。因此，我们旨在研究胰腺炎后GRP与AGM之间的关联。
采集空腹血样以检测GRP、血糖、胰岛素、胰淀素、胰高血糖素、胰多肽（PP）、生长抑素、胆囊收缩素、胃抑制肽（GIP）、胃泌素、胃饥饿素、甘丙肽、胰高血糖素样肽-1和2、胃动素、肽YY（PYY）、促胰液素、血管活性肠肽、肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白（MCP）-1和白细胞介素-6。进行了修正泊松回归分析和线性回归分析。使用四种统计模型来调整人口统计学、代谢和胰腺炎相关的危险因素。
共招募了83例胰腺炎发作后的个体。GRP与AGM显著相关，在所有四种模型中均一致（P趋势<0.05），且空腹血糖对GRP变异的贡献率为17%。此外，GRP与胰高血糖素（P<0.003）、MCP-1（P<0.025）和TNF-α（P<0.025）显著相关，在所有四种模型中均一致。GRP在三种模型中也与PP和PYY显著相关（两者P均<0.030），在一种模型中与GIP和甘丙肽显著相关（分别为P = 0.001和0.024）。GRP与其他胰腺和肠道激素之间的关联不显著。
胰腺炎后AGM患者的GRP显著升高，且与促炎细胞因子以及某些胰腺和肠道激素水平升高有关。现在有必要进行详细的机制研究，以探讨GRP在胰腺炎后葡萄糖稳态紊乱中的确切作用。
