Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Cytokines; Gastrin-releasing peptide; Gut hormones; Pancreatic hormones; Post-pancreatitis diabetes mellitus.

Figure 1

Association between GRP and abnormal glucose metabolism in patients after acute pancreatitis. GRP: gastrin-releasing peptide; CI: confidence interval; PR: prevalence ratio.

Figure 2

Associations between GRP and FBG (a) and HbA1c (b). FBG: fasting blood glucose; GRP: gastrin-releasing peptide; HbA1c: glycated hemoglobin A1c.