glucagon-like-peptide-1-(7-36)amide and Postoperative-Complications

An alteration of the enteroinsular axis (EIA) may be an important etiologic factor in postsurgical changes in gastrointestinal (GI) function. In this review, we present recent works, both from our laboratory and others, on how changes in the EIA function may be involved in postsurgical GI complications, especially late dumping syndrome (LDS). We found no or minimal direct role for vagal signals in the control of gastric inhibitory polypeptide (GIP) and enteroglucagon secretion, which regulate EIA function. In gastrectomized patients, it is suggested that the hypersecretion of glicentin and glucagon-like peptide-1 (GLP-1) induced by a rapid arrival of nutrients to the distal gut suppresses glucagon secretion and may be a cause of LDS. In patients who underwent proctocolectomy, we observed no significant postoperative changes in EIA function, although there are some conflicting reports. It seems unlikely that ordinary pancreaticobiliary diversion would cause a significant change in EIA function after an oral glucose load. Our experimental model of ileojejunal transposition produced marked hypersecretion of incretin secreted from the distal gut, which may alter EIA function. Further elucidation of the regulatory mechanism of EIA may provide a new strategy for the medical and surgical treatment of LDS.

Topics: Digestive System Surgical Procedures; Dumping Syndrome; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Neurotransmitter Agents; Pancreas; Peptide Fragments; Postoperative Complications

Glucagon-like peptide 1 (GLP-1[7-36 amide]) is an incretin hormone primarily synthesized in the lower gut (ileum, colon/rectum). Nevertheless, there is an early increment in plasma GLP-1 immediately after ingesting glucose or mixed meals, before nutrients have entered GLP-1 rich intestinal regions. The responsible signalling pathway between the upper and lower gut is not clear. It was the aim of this study to see, whether small intestinal resection or colonectomy changes GLP-1[7-36 amide] release after oral glucose. In eight healthy controls, in seven patients with inactive Crohn's disease (no surgery), in nine patients each after primarily jejunal or ileal small intestinal resections, and in six colonectomized patients not different in age (p = 0.10), body-mass-index (p = 0.24), waist-hip-ratio (p = 0.43), and HbA1c (p = 0.22), oral glucose tolerance tests (75 g) were performed in the fasting state. GLP-1[7-36 amide], insulin C-peptide, GIP and glucagon (specific (RIAs) were measured over 240 min.. Repeated measures ANOVA, t-test (significance: p < 0.05). A clear and early (peak: 15-30 min) GLP-1[7-36 amide] response was observed in all subjects, without any significant difference between gut-resected and control groups (p = 0.95). There were no significant differences in oral glucose tolerance (p = 0.21) or in the suppression of pancreatic glucagon (p = 0.36). Colonectomized patients had a higher insulin (p = 0.011) and C-peptide (p = 0.0023) response in comparison to all other groups. GIP responses also were higher in the colonectomized patients (p = 0.0005). Inactive Crohn's disease and resections of the small intestine as well as proctocolectomy did not change overall GLP-1[7-36 amide] responses and especially not the early increment after oral glucose. This may indicate release of GLP-1[7-36 amide] after oral glucose from the small number of GLP-1[7-36 amide] producing L-cells in the upper gut rather than from the main source in the ileum, colon and rectum. Colonectomized patients are characterized by insulin hypersecretion, which in combination with their normal oral glucose tolerance possibly indicates a reduced insulin sensitivity in this patient group. GIP may play a role in mediating insulin hypersecretion in these patients.

Topics: Adult; Aged; C-Peptide; Colectomy; Crohn Disease; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Insulin; Intestine, Large; Intestine, Small; Male; Middle Aged; Peptide Fragments; Postoperative Complications